Wersja z 2019–11–20

Wirusy
i twory wirusopodobne

Wirusy to skomplikowane cząsteczki (nukleoproteiny) lub zespoły cząsteczek związków organicznych, niemające struktury komórkowej, zdolne do reprodukcji. Wirusy złożone są z białek i jednego kwasu nukleinowego: albo DNA, albo RNA. Na ogół nie wydzielają enzymów. Zdolne są do replikacji biernej, tzn. są namnażane przy pomocy struktur i substancji zawartych w żywych komórkach.

Wirusy klasyfikuje się ze względu na rodzaj kwasu nukleinowego, liczbę nici, a także to, czy nić jest kodująca (+) czy niekodująca (−). Nić jest kodująca wówczas, gdy sekwencja budujących ją nukleotydów odpowiada sekwencji nukleotydów mRNA, stanowiącego matrycę do translacji (syntezy białek).

Pod względem liczby nici kwasu nukleinowego wirusy dzielą się na ds i ss.
ds = double-stranded, dwuniciowe
ss = single-stranded, jednoniciowe

Zgodnie z klasyfikacją Baltimore’a wyróżnia się 7 grup wirusów, numerowanych liczbami rzymskimi.

W cyklu życiowym wirusów występują następujące procesy:
- replikacja DNA (DNA → DNA) w grupach I, II,
- transkrypcja (DNA → RNA) w grupach I, II, VI, VII,
procesy nietypowe:
- odwrotna transkrypcja (RNA → DNA) w grupach VI, VII,
- replikacja RNA (na RNA) w grupach III, IV, V, VII.

Odwrotna transkrypcja i replikacja RNA to procesy charakterystyczne dla wirusów, niewystępujące u organizmów żywych.

Charakterystyka poszczególnych grup wirusów

I. Wirusy dsDNA (z DNA dwuniciowym)

Tu należą na przykład:

Rodzina: Herpesviridae – herpeswirusy
- Simplexvirus – wirus opryszczki pospolitej
- Varicellovirus – wirus ospy wietrznej i półpaśca
Rodzina: Adenoviridae – adenowirusy
- Mastadenovirus – wirus zapalenia migdałków i zakażenia dróg oddechowych u dzieci
Rodzina: Myoviridae – bakteriofagi parzyste
- T4virus – bakteriofag T4 (ma geny z intronami)
Rodzina: Poxviridae – pokswirusy
- Orthopoxvirus – wirus ospy prawdziwej
Rodzina: Pandoraviridae – pandorawirusy
- Pandoravirus (bardzo duży, większy od bakterii, a nawet niektórych eukariontów; ma niewiele genów podobnych do jakichkolwiek genów znanych organizmów)
Rodzina: Pithoviridae – pitowirusy
- Pithovirus (największy znany wirus, pasożytujący na amebach)

Group I: Double-stranded DNA viruses
Main article: dsDNA virus
These types of viruses must enter the host nucleus before they are able to replicate. Furthermore, these viruses require host cell polymerases to replicate the viral genome and, hence, are highly dependent on the cell cycle. Proper infection and production of progeny requires that the cell be in replication, as it is during replication that the cell's polymerases are active. The virus may induce the cell to forcefully undergo cell division, which may lead to transformation of the cell and, ultimately, cancer. Examples include Herpesviridae, Adenoviridae, and Papovaviridae.

There is only one well-studied example in which a class 1 virus is not replicating within the nucleus: the Poxvirus family, a highly pathogenic virus that infects vertebrates and includes the smallpox virus.

The mRNA is transcribed regularly from viral DNA using the host's RNA polymerase II. This produces two types of mRNA's: 1) early mRNA, transcribed prior to the synthesis of viral DNA, and 2) late mRNA, transcribed from progeny DNA.

Group II: Single-stranded DNA viruses
Main article: ssDNA virus
Viruses in this category include the Anelloviridae, Circoviridae, and Parvoviridae (which infect vertebrates), the Geminiviridae and Nanoviridae (which infect plants), and the Microviridae (which infect prokaryotes). Most of them have circular genomes (the parvoviruses are the only known exception). Eukaryote-infecting viruses replicate mostly within the nucleus – usually via a rolling circle mechanism, forming double-stranded DNA intermediate in the process. A prevalent but asymptomatic human Anellovirus, called Transfusion Transmitted Virus (TTV), is included within this classification.

Group III: Double-stranded RNA viruses
Main article: dsRNA virus
As with most RNA viruses, this class replicates in the “Core” capsid that is in cytoplasm, not having to use the host replication polymerases to as much a degree as DNA viruses. This family is also not as well-studied as the rest and includes 2 major families, the Reoviridae and Birnaviridae. Replication is monocistronic and includes individual, segmented genomes, meaning that each of the genes codes for only one protein, unlike other viruses that exhibit more complex translation.

Group IV & V: Single-stranded RNA viruses
The ssRNA viruses belong to Class IV or V of the Baltimore classification. They could be grouped into positive sense or negative sense according to the sense of polarity of RNA. The single stranded RNA is the common feature of these viruses. The replication of viruses happens in the cytoplasm or nucleus (for segmented class V viruses). Class IV and V ssRNA viruses do not depend as heavily as DNA viruses on the cell cycle.[clarification needed]

Group IV: Single-stranded RNA viruses – Positive-sense
Main article: positive-sense ssRNA virus
The positive-sense RNA viruses and indeed all RNA defined as positive-sense can be directly accessed by the host ribosomes to immediately form proteins. These can be divided into two groups, both of which reproduce in the cytoplasm:

Viruses with polycistronic mRNA where the genome RNA forms the mRNA and is translated into a polyprotein product that is subsequently cleaved to form the mature proteins. This means that the gene can utilize a few methods in which to produce proteins from the same strand of RNA, all in the sake of reducing the size of its gene.
Viruses with complex transcription, for which subgenomic mRNAs, ribosomal frameshifting, and proteolytic processing of polyproteins may be used. All of which are different mechanisms with which to produce proteins from the same strand of RNA.
Examples of this class include the families Astroviridae, Caliciviridae, Coronaviridae, Flaviviridae, Picornaviridae, Arteriviridae, and Togaviridae.

Group V: Single-stranded RNA viruses – Negative-sense
Main article: negative-sense ssRNA virus
The negative-sense RNA viruses and indeed all genes defined as negative-sense cannot be directly accessed by host ribosomes to immediately form proteins. Instead, they must be transcribed by viral polymerases into a “readable” form, which is the positive-sense reciprocal. These can also be divided into two groups:

Viruses containing nonsegmented genomes for which the first step in replication is transcription from the (−)-stranded genome by the viral RNA-dependent RNA polymerase to yield monocistronic mRNAs that code for the various viral proteins. A positive-sense genome copy is then produced that serves as template for production of the (−)-strand genome. Replication is within the cytoplasm.
Viruses with segmented genomes for which replication occurs in the nucleus and for which the viral RNA-dependent RNA polymerase produces monocistronic mRNAs from each genome segment. The largest difference between the two is the location of replication.
Examples in this class include the families Arenaviridae, Orthomyxoviridae, Paramyxoviridae, Bunyaviridae, Filoviridae, and Rhabdoviridae (the latter of which includes the rabies virus).

Group VI: Positive-sense single-stranded RNA viruses that replicate through a DNA intermediate
Main article: ssRNA-RT virus
A well-studied family of this class of viruses include the retroviruses. One defining feature is the use of reverse transcriptase to convert the positive-sense RNA into DNA. Instead of using the RNA for templates of proteins, they use DNA to create the templates, which is spliced into the host genome using integrase. Replication can then commence with the help of the host cell's polymerases.

Group VII: Double-stranded DNA viruses that replicate through a single-stranded RNA intermediate
Main article: dsDNA-RT virus
The pregenome RNA serves as template for the viral reverse transcriptase for production of the DNA genom Example:-hapadena virus

Wykrzyknikiem oznaczyłem procesy nietypowe dla organizmów żywych (a może po prostu nieznane poza światem wirusów)
Jak dla mnie najciekawszą grupą jest VII, czyli wirusy DNA/RNA (nie mylić z wirusami RNA/DNA). W swoich wirionach mają normalne dwuniciowe DNA, ale nie prowadzą na nim normalnej transkrypcji do mRNA, tylko najpierw produkują jednoniciowe RNA, i dopiero na matrycy
tego RNA produkują mRNA
ds i ss to skróty ang. double-stranded i single-stranded
W wypadku wirusów ssDNA nie ma znaczenia, czy nić jest + czy – (co więcej, jedna nić dla niektórych genów może być kodująca, dla innych matrycowa), bo przed rozpoczęciem transkrypcji odtwarzana jest druga nić DNA i wewnątrz komórki wirus ma DNA dwuniciowe
(grupa II)

Grupa VII ma też odwrotną transkrypcję. Cykl lityczny tych wirusów wygląda tak:
1. Do komórki wnika dsDNA wirusa.
2. W procesie transkrypcji powstaje ssRNA wirusa.
3. Na tym ssRNA zachodzi replikacja RNA na mRNA (proces wirusowy)
4. To powstałe mRNA (drugiego rzędu) służy jako matryca dla syntezy białek wirusa (na rybosomach gospodarza).
5. Nie zachodzi replikacja dsDNA wirusowego! I to jest właśnie najdziwniejsze!
6. Pierwsze powstałe ssRNA ulega też replikacji, czyli z ssRNA tworzone jest ssRNA, i w ten sposób wirus się namnaża.
7. Na koniec działa odwrotna transkryptaza, i z namnożonego ssRNA powstaje dsDNA.
8. To dsDNA nie ulega ani replikacji, ani transkrypcji, tylko otacza się białkami i opuszcza komórkę gospodarza.

Innymi słowy, grupa VII to wirusy, które w swoich wirionach mają co prawda DNA, ale nie potrafią go zreplikować. Muszą w tym celu wytworzyć RNA, replikują to RNA w sposób obcy dla normalnych organizmów (RNA → RNA), i dopiero po uzyskaniu dostatecznej ilości kopii na bazie tego zreplikowanego RNA odtwarzają własne DNA
Do grupy VII należy wirus żółtaczki zakaźnej typu B
A, i jeszcze taka uwaga. Retrowirusy to POTOCZNA nazwa grup VI i VII łącznie, bo są to wirusy mające odwrotną transkrypcję w swoim cyklu litycznym. Jednak POPRAWNA nazwa retrowirusy odnosi się do jednej z podgrup grupy VI (czyli w waszych podręcznikach piszą bzdury)
Grupy VI i VII łącznie tworzą rząd Ortervirales. Do grupy VI (wirusy w typie HIV pod względem przebiegu cyklu litycznego) należą rodziny Belpaoviridae, Metaviridae, Pseudoviridae i Retroviridae – i tylko tę ostatnią rodzinę nazywamy retrowirusami. Inaczej mówiąc, obok retrowirusów odwrotną transkrypcję mają także belpaowirusy, metawirusy i pseudowirusy. HIV oczywiście jest retrowirusem.

Grupa VII to rodzina Caulimoviridae (i tu należy wirus WZW B)
A jak widzę, wirus WZW B zaliczany jest ostatnio do odrębnej rodziny Hepadnaviridae

[Przyłóżmy] paradygmat cybernetyczny do wiroidów, czyli nagich cząsteczek RNA pasożytujących na roślinach. Potrafią one dostać się do komórek swego gospodarza i tam indukować intensywną produkcję własnych kopii, co zaburza funkcjonowanie komórki (ogołaca ją z energii i substancji budulcowych), prowadząc do jej śmierci. Wiroidy nie mają, co prawda, podobnie jak wirusy, „własnego” metabolizmu. Można by się więc spierać, czy są w posiadaniu „własnego” systemu sprzężeń zwrotnych ujemnych. Byłaby to jednak dyskusja czysto akademicka. Dla nas ważne jest, że wiroidy potrafią „wejść” w system sprzężeń zwrotnych ujemnych komórki gospodarza i przestawić go na inne tory, zmieniając parametr, którego wartość jest optymalizowana. Ten optymalizowany parametr to po prostu (możliwie duża) liczba kopii danego wiroida, natomiast zaniedbana zostaje regulacja takich parametrów, jak stężenie ATP, substancji odżywczych etc. co w końcu prowadzi do śmierci komórki i uwolnienia wiroidów (nagich, kolistych cząsteczek RNA), które mogą następnie infekować następne komórki. Cała struktura wiroida, wynikająca z sekwencji nukleotydów w nici RNA, jest przystosowana do wnikania do komórek gospodarza i przestawiania ich metabolizmu na namnażanie cząsteczek wiroida preferencyjne w stosunku do syntezy własnych kwasów nukleinowych komórek i w ogóle w stosunku do wszelkich innych procesów Tożsamość (sekwencja nukleotydów) wiroida może ewoluować, zwiększając jego skuteczność infekcyjną oraz umożliwiając mu zainfekowanie innych gatunków roślin.

Wszystkie „czynności życiowe” wiroida wykonywane są przez enzymy gospodarza, kosztem jego energii i substancji budulcowych. Owo „scedowanie” na żywiciela części sieci sprzężeń zwrotnych ujemnych potrzebnych pasożytowi do przeżycia jest typowe dla układu pasożyt – żywiciel. W zasadzie, stanowi ono właśnie o istocie pasożytnictwa. U wiroidów scedowanie to przybrało jednak formę skrajną – właściwie wszystkie mechanizmy regulacyjne zostały „przerzucone” na gospodarza, podczas gdy zadaniem pasożyta jest jedynie „wejść” w system sprzężeń zwrotnych ujemnych żywiciela i przestawić go na realizowanie własnego namnażania. Jako że wiroidy są ewidentnie „intencjonalnie” nakierowane na wykonanie tego zadania, z cybernetycznego punktu widzenia należy je uznać za ewoluony.

Cały spowodowany przez wiroidy ciąg zdarzeń jest więc ściśle celowy i prowadzi do namnażania cząstek wiroida oraz infekcji następnych komórek lub osobników gospodarza. Zjawisko takie w żadnym razie nie występuje u prionów. W swojej formie „normalnej” priony pełnią najprawdopodobniej jakąś użyteczną funkcję w organizmie gospodarza (są przecież kodowane w jego DNA), natomiast szkodliwość ich formy „infekcyjnej” jest po prostu przypadkiem, pułapką ewolucyjną wytwarzającego je organizmu, czymś (ale to dosyć daleka analogia) w rodzaju autoalergii[ 8 ]. Nie mamy żadnych podstaw, aby sądzić (i wydaje się to niemożliwe z przyczyn zasadniczych), że struktura prionów została przez ewolucję „udoskonalona” w celu zwiększenia ich infektywności. Nie stanowią one bowiem „podmiotu” dla ewolucji, choćby dlatego, że nie potrafią przekazać swemu „potomstwu” informacji o własnej strukturze (sekwencji aminokwasów), a więc zachować ciągłości w czasie własnej tożsamości. Informacja ta znajduje się bowiem nie w nich samych, ale w jądrze komórkowym, na które nie mają wpływu. De facto, namnażaniu ulegają przecież nie priony (których ilość pozostaje stała w czasie), a jedynie ich konformacja infekcyjna (kosztem formy normalnej). Priony nie są zatem w żadnym razie ewoluonami, w przeciwieństwie do wiroidów. Niemniej, postawienie obok siebie prionów i wiroidów (oba fenomeny reprezentują pojedynczą makromolekułę chemiczną) znacznie zmniejsza przepaść ziejącą, zdawałoby się, pomiędzy życiem i kamienną lawiną.

Jeżeli status ewoluonów przyznamy został wiroidom, to z pewnością należy się on także wirusom, których jednostki – wiriony – to cząsteczki RNA lub DNA „zamknięte w chroniącej je i ułatwiającej proces infekcji otoczce białkowej. Cząsteczka kwasu nukleinowego w wirionie jest znacznie większa, niż nić RNA wiroidu. Koduje ona kilka białek, w tym białka otoczki oraz białka uczestniczące w powielaniu wirusowej nici DNA lub RNA w komórce gospodarza, a także biorące udział w syntezie białek otoczki wirusa. Wirusy wykazują już jakby zaczątki własnej sieci sprzężeń zwrotnych ujemnych. Bakteriofagi aktywnie wstrzykują swoją nić kwasu nukleinowego do komórki bakterii, a wiele wirusów koduje własne enzymy, optymalizujące szybkość namnażania wirionów potomnych w komórce gospodarza. Generalnie jednak, z punktu widzenia paradygmatu cybernetycznego, wirusy należałoby postawić w ścisłym sąsiedztwie wiroidów.

Inny ciekawy casus, w pewnym sensie pośredni pomiędzy prionami z jednej strony, a wiroidami i wirusami – z drugiej, stanowią nowotwory, a w szczególności nowotwory złośliwe. Akt transformacji nowotworowej normalnej komórki można interpretować w kategoriach cybernetycznych jako „wyłamanie się tej komórki spod realizacji nadrzędnego celu całego organizmu i narzucenie sobie własnego celu nadrzędnego, czyli po prostu własnej ekspansji. Nowotwór nie „wie”, że jego żywot skończy się wraz ze śmiercią całego organizmu (zresztą nie zawsze tak jest – wiele linii nowotworowych hoduje się obecnie dla celów naukowych!), tak jak dinozaury nie „wiedziały”, że wyginą na skutek upadku meteorytu. Oba przypadki różni oczywiście skala czasowa – ale niewiele więcej. Często uważamy raka za zjawisko zupełnie bezsensowne, w przeciwieństwie do życia. Jest to jednak ułuda ludzkiego umysłu, ferowana przez nasze skłonności do antropocentryzmu. Nowotwór nie jest mniej (lub bardziej) sensowny, niż życie w ogóle (ściślej: różnica jest jedynie ilościowa, lecz nie jakościowa). Komórki nowotworowe nie posiadają po prostu odpowiednich mechanizmów, żeby zapewnić sobie przetrwanie po śmierci organizmu, który opanowały. Jednak w „środowisku” organizmu radzą sobie nie gorzej, niż bakterie na pożywce. To, że komórki nowotworowe nie mają czasu na większą ewolucję i „doskonalenie się” (aż skóra cierpnie na samą myśl o takiej możliwości) spowodowane jest bardzo ograniczoną pojemnością ich „środowiska”. Nie są one zatem w stanie wytworzyć na czas dostatecznie skomplikowanej sieci sprzężeń zwrotnych ujemnych (sprzężenia zwrotnego dodatniego im nie brakuje). Innymi słowy, komórki nowotworowe nie zdążą „przystosować się” do swojej szeroko rozumianej „niszy ekologicznej”. Zauważmy iż ewolucja „normalnych” pasożytów zmierza w kierunku zmniejszenia ich szkodliwości dla organizmu gospodarza – nie opłaca się im się bowiem zabijać swego żywiciela. Nowotwór różni się oczywiście od „normalnego” pasożyta niemożnością zarażenia innego organizmu żywicielskiego. Jeżeli jednak komórka nowotworowa wytwarza w krótkim czasie swego istnienia przynajmniej pewne celowe mechanizmy (sprzężenia zwrotne ujemne) powodujące niewrażliwość na układ odpornościowy (immunologiczny) lub inne reakcje obronne organizmu, a więc zapewniające jej przeżycie i rozwój w jej środowisku (czyli organizmie), to z formalnego punktu widzenia jest ona osobnikiem cybernetycznym (ewoluonem). Jak wspomniałem, w obrębie paradygmatu cybernetycznego nowotwory lokują się w pewnym sensie gdzieś pomiędzy prionami a wiroidami i wirusami. Nowotwory posiadają sieć sprzężeń zwrotnych dodatnich zapewniających im ekspansję w tymczasowym (ale to kwestia umownej skali czasowej – istnienie życia na kuli Ziemskiej, jeżeli liczone w miliardach lat, także jest tymczasowe), ograniczonym środowisku organizmu żywego. Charakteryzują je także zapewne pierwociny ewolucji (np. presja układu immunologicznego mogłaby premiować „najlepiej przystosowane” komórki nowotworowe) – gdyby pozwolić im żyć dostatecznie długo, z pewnością zaczęłyby one „normalnie” ewoluować. Stawia to nowotwory „wyżej” od prionów, które nie są w posiadaniu żadnego układu sprzężeń zwrotnych ujemnych. Nowotwory nie potrafią jednak przetrwać i rozprzestrzeniać się w szerszym i bardziej trwałym środowisku, jaki stanowi populacja osobników gatunku żywicielskiego, co charakteryzuje wiroidy i wirusy, mogące przenosić się z jednego osobnika na inny. Dowodzi to większego stopnia „ożywienia” tych ostatnich, chociaż pod względem skomplikowania struktury wirusy i wiroidy znacznie ustępują komórkom nowotworowym. Liczy się jednak przede wszystkim kryterium cybernetyczne.

Witam serdecznie :)

Muszę na wstępie wspomnieć, że jestem przeogromnie zadowolony, że trafiłem na Pana publikację. Od lat interesuję się tematem i przyznam, że w szkole uczono mnie klasyfikacji jeszcze w stylu 5 królestw. Coraz szybciej zachodzące zmiany w taksonomii spowodowały, że nie byłem w stanie się w tym wszystkim połapać, a polskojęzycznego źródła, które opisywałoby te wszystkie zmiany nie mogłem w żaden sposób znaleźć. Aż w końcu udało mi się trafić na Pana publikację – idealne zestawienie w jaki sposób podział się zmieniał (co dokąd powędrowało itp.), jest także o wirusach, dobrze znanych wiroidach, prionach, ale także o kontrowersyjnych i dotąd nierozstrzygniętych nanobów i nanobakterii.
Jeśli można, chciałbym tylko zasugerować, a także poprosić bardzo Pana o drobne uzupełnienie w publikacji terminów (myślę, że będą one przydatne dla wielu osób czytających publikację, gdyż wiem to po sobie:), a jedynie ich mi tutaj brakuje – myślę, że w miejscu, gdzie wymienia Pan wiroidy, priony itp. warto byłoby dopisać o strukturach zależnych od innych wirusów (wirusów pomocniczych), tj. tzw. wirusach satelitarnych oraz tzw. defektywnych cząsteczkach interferujących, z których obie wymagają do replikacji wirusa pomocniczego, są więc pewną specyficzną dodatkową strukturą. W dodatku, niemal nieopisaną w polskich publikacjach. Sądzę więc, że napomknięcie o nich w Pana publikacji, choćby na zasadzie wtrącenia jak o prionach, będzie bardzo użyteczne i zainteresowana osoba, która natrafi na tę kwestię będzie miała szansę poznać te terminy i dalej szukać (ja miałem tak z nanobami :).
Czy mógłbym więc Pana prosić o zamieszczenie choćby luźnego napomknięcia o tych dwóch strukturach?, które również z organizmami pewien (podobny do wiroidów czy prionów) związek mają
Pozwolę sobie również przy okazji bardzo podziękować za tę publikację. Jest mi ona niezwykle pomocna (co prawda w zakresie stricte hobbystycznym:), ale no wręcz zbawienna!
Z poważaniem i ogromnym podziękowaniem,

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Nie znaleziono wirusów w tej wiadomości.
Sprawdzone przez AVG – www.avg.com
Wersja: 2015.0.6081 / Baza danych wirusów: 4392/10309 – Data wydania: 2015–07–26

Jeszcze pozwolę sobie tylko uzupełnić – bardzo możliwe, że rozsądnym byłoby po prostu przy wirusach dopisać, że obejmują także satelity i defektywne cząstki interferujące, gdyż są to przecież wirusy satelitarne oraz (czasem tak nazywane) defektywne wirusy interferujące. 1 z tych 2 sposobów uwzględnienia ich (czy to wliczając do wirusów, czy to wymienić jako nieuwzględnione obok wiroidów, prionów itp.) myślę, że będzie rozsądny, a także przydatny dla czytających.
Dziękuję :)

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Dnia 26 lipca 2015 0:35 Adrian Drynda kylie1@o2.pl napisał(a):

Witam serdecznie :)

Muszę na wstępie wspomnieć, że jestem przeogromnie zadowolony, że trafiłem na Pana publikację. Od lat interesuję się tematem i przyznam, że w szkole uczono mnie klasyfikacji jeszcze w stylu 5 królestw. Coraz szybciej zachodzące zmiany w taksonomii spowodowały, że nie byłem w stanie się w tym wszystkim połapać, a polskojęzycznego źródła, które opisywałoby te wszystkie zmiany nie mogłem w żaden sposób znaleźć. Aż w końcu udało mi się trafić na Pana publikację – idealne zestawienie w jaki sposób podział się zmieniał (co dokąd powędrowało itp.), jest także o wirusach, dobrze znanych wiroidach, prionach, ale także o kontrowersyjnych i dotąd nierozstrzygniętych nanobów i nanobakterii.
Jeśli można, chciałbym tylko zasugerować, a także poprosić bardzo Pana o drobne uzupełnienie w publikacji terminów (myślę, że będą one przydatne dla wielu osób czytających publikację, gdyż wiem to po sobie:), a jedynie ich mi tutaj brakuje – myślę, że w miejscu, gdzie wymienia Pan wiroidy, priony itp. warto byłoby dopisać o strukturach zależnych od innych wirusów (wirusów pomocniczych), tj. tzw. wirusach satelitarnych oraz tzw. defektywnych cząsteczkach interferujących, z których obie wymagają do replikacji wirusa pomocniczego, są więc pewną specyficzną dodatkową strukturą. W dodatku, niemal nieopisaną w polskich publikacjach. Sądzę więc, że napomknięcie o nich w Pana publikacji, choćby na zasadzie wtrącenia jak o prionach, będzie bardzo użyteczne i zainteresowana osoba, która natrafi na tę kwestię będzie miała szansę poznać te terminy i dalej szukać (ja miałem tak z nanobami :).
Czy mógłbym więc Pana prosić o zamieszczenie choćby luźnego napomknięcia o tych dwóch strukturach?, które również z organizmami pewien (podobny do wiroidów czy prionów) związek mają
Pozwolę sobie również przy okazji bardzo podziękować za tę publikację. Jest mi ona niezwykle pomocna (co prawda w zakresie stricte hobbystycznym:), ale no wręcz zbawienna!
Z poważaniem i ogromnym podziękowaniem,

AD

Nie znaleziono wirusów w tej wiadomości.
Sprawdzone przez AVG – www.avg.com
Wersja: 2015.0.6081 / Baza danych wirusów: 4392/10323 – Data wydania: 2015–07–28

Jeszcze (przepraszam, że tak podzielone, ale zapomniałem uwzględnić to wcześniej) – jeśli można prosić o zawarcie również tekście napomknięcia o hipotetycznym (potencjalnym) sztucznym życiu (które co prawda jeszcze nie istnieje, jest w fazie hipotetyczności, jednak w wielu opracowaniach padają argumenty, że byłoby ono podobnie żywe jak wirusy i wiroidy). Myślę, że również przydatne czytelnikom będzie napomknięcie, iż próby jego stworzenia istnieją (czytelnik będzie mógł wtedy poszukać większej ilości informacji w tym temacie). Proszę mi wybaczyć aż 3 maile, jednak chciałem te 2 wątki zawrzeć.

Jeszcze raz dziękuję za świetną, przydatną publikację, prosząc o uwzględnienie tych 2 (satelity+defektywne cząstki oraz hipotetyczne sztuczne życie) w tekście, choćby w formie napomknięcia. :)

Pozdrawiam jeszcze raz.

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Dnia 26 lipca 2015 12:27 Adrian Drynda kylie1@o2.pl napisał(a):

Jeszcze pozwolę sobie tylko uzupełnić – bardzo możliwe, że rozsądnym byłoby po prostu przy wirusach dopisać, że obejmują także satelity i defektywne cząstki interferujące, gdyż są to przecież wirusy satelitarne oraz (czasem tak nazywane) defektywne wirusy interferujące. 1 z tych 2 sposobów uwzględnienia ich (czy to wliczając do wirusów, czy to wymienić jako nieuwzględnione obok wiroidów, prionów itp.) myślę, że będzie rozsądny, a także przydatny dla czytających.
Dziękuję :)

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Dnia 26 lipca 2015 0:35 Adrian Drynda kylie1@o2.pl napisał(a):

Witam serdecznie :)

Muszę na wstępie wspomnieć, że jestem przeogromnie zadowolony, że trafiłem na Pana publikację. Od lat interesuję się tematem i przyznam, że w szkole uczono mnie klasyfikacji jeszcze w stylu 5 królestw. Coraz szybciej zachodzące zmiany w taksonomii spowodowały, że nie byłem w stanie się w tym wszystkim połapać, a polskojęzycznego źródła, które opisywałoby te wszystkie zmiany nie mogłem w żaden sposób znaleźć. Aż w końcu udało mi się trafić na Pana publikację – idealne zestawienie w jaki sposób podział się zmieniał (co dokąd powędrowało itp.), jest także o wirusach, dobrze znanych wiroidach, prionach, ale także o kontrowersyjnych i dotąd nierozstrzygniętych nanobów i nanobakterii.
Jeśli można, chciałbym tylko zasugerować, a także poprosić bardzo Pana o drobne uzupełnienie w publikacji terminów (myślę, że będą one przydatne dla wielu osób czytających publikację, gdyż wiem to po sobie:), a jedynie ich mi tutaj brakuje – myślę, że w miejscu, gdzie wymienia Pan wiroidy, priony itp. warto byłoby dopisać o strukturach zależnych od innych wirusów (wirusów pomocniczych), tj. tzw. wirusach satelitarnych oraz tzw. defektywnych cząsteczkach interferujących, z których obie wymagają do replikacji wirusa pomocniczego, są więc pewną specyficzną dodatkową strukturą. W dodatku, niemal nieopisaną w polskich publikacjach. Sądzę więc, że napomknięcie o nich w Pana publikacji, choćby na zasadzie wtrącenia jak o prionach, będzie bardzo użyteczne i zainteresowana osoba, która natrafi na tę kwestię będzie miała szansę poznać te terminy i dalej szukać (ja miałem tak z nanobami :).
Czy mógłbym więc Pana prosić o zamieszczenie choćby luźnego napomknięcia o tych dwóch strukturach?, które również z organizmami pewien (podobny do wiroidów czy prionów) związek mają
Pozwolę sobie również przy okazji bardzo podziękować za tę publikację. Jest mi ona niezwykle pomocna (co prawda w zakresie stricte hobbystycznym:), ale no wręcz zbawienna!
Z poważaniem i ogromnym podziękowaniem,

AD

Nie znaleziono wirusów w tej wiadomości.
Sprawdzone przez AVG – www.avg.com
Wersja: 2015.0.6081 / Baza danych wirusów: 4392/10323 – Data wydania: 2015–07–28

Wielce Szanowny Panie Grzegorzu,

mając nadzieję, że jeszcze moja korespondencja nie została odczytana, chciałbym uporządkować to, co w niej zawarte. Proszę mi wybaczyć, że było to tak chaotyczne i rozdzielone, jest to absolutnie moja wina, proszę tego nie traktować jako brak kultury z mojej strony. Po prostu nieumiejętnie do tego podszedłem. Przepraszam za to :)

Otóż, skoro napisano o (hipotetycznych/rzekomych wciąż, gdyż z punktu widzenia biologii jeszcze będących nierozstrzygniętym problemem) nanobach i nanobakteriach, warto moim zdaniem dodać również hipotetyczne/potencjalne „sztuczne życie”, które gdyby się pojawiło, zgodnie z wieloma klasyfikacjami – podobnie jak wirusy czy wiroidy – byłoby traktowane jako życie. Przy okazji, warto pamiętać, że coraz częściej także wirusoidy zaczynają być wraz z wirusami traktowane jako 4. domena ewolucyjna organizmów i dzielone na rodziny (Pospiviroidae oraz Avsunvirioidae).

Również przy wymienieniu takich struktur jak wiroidy czy priony, warto napomknąć moim zdaniem o satelitach (jest to pojęcie nieco szersze, bo obejmujące nie tylko tzw. wirusy satelitarne, ale i tzw. satelitarne kwasy nukleinowe, do których zaliczają się m.in. tzw. wirusoidy), które wraz z wiroidami oraz prionami są zaliczane do tzw. czynników subwirusowych, oraz o tzw. defektywnych cząsteczkach interferujących, które jako pewne specyficzne struktury organiczne zależne od wirusów podobnie jak satelity wymagają pomocy innego wirusa (pomocniczego) do replikacji.

Myślę, że choć luźne napomknięcie tych kwestii (potencjalne sztuczne życie, satelity i DIPy) będzie uzupełnieniem Pana publikacji oraz informacją, mogącą być przydatną dla czytelników, którzy zechcą dalej szukać. :)

Bardzo jeszcze raz przepraszam za 4-mailową formę, mój błąd, tu postarałem się jednak zebrać to w całość i dziękuję za odczytanie maila. Czy można prosić o uwzględnienie tych 2 (w zasadzie 3) zagadnień w artykule „Klasyfikacja istot żywych” Pana autorstwa?

Z poważaniem i uznaniem,

AD

Dnia 26 lipca 2015 12:52 Adrian Drynda kylie1@o2.pl napisał(a):

Jeszcze (przepraszam, że tak podzielone, ale zapomniałem uwzględnić to wcześniej) – jeśli można prosić o zawarcie również tekście napomknięcia o hipotetycznym (potencjalnym) sztucznym życiu (które co prawda jeszcze nie istnieje, jest w fazie hipotetyczności, jednak w wielu opracowaniach padają argumenty, że byłoby ono podobnie żywe jak wirusy i wiroidy). Myślę, że również przydatne czytelnikom będzie napomknięcie, iż próby jego stworzenia istnieją (czytelnik będzie mógł wtedy poszukać większej ilości informacji w tym temacie). Proszę mi wybaczyć aż 3 maile, jednak chciałem te 2 wątki zawrzeć.

Jeszcze raz dziękuję za świetną, przydatną publikację, prosząc o uwzględnienie tych 2 (satelity+defektywne cząstki oraz hipotetyczne sztuczne życie) w tekście, choćby w formie napomknięcia. :)

Pozdrawiam jeszcze raz.

AD

Dnia 26 lipca 2015 12:27 Adrian Drynda kylie1@o2.pl napisał(a):

Jeszcze pozwolę sobie tylko uzupełnić – bardzo możliwe, że rozsądnym byłoby po prostu przy wirusach dopisać, że obejmują także satelity i defektywne cząstki interferujące, gdyż są to przecież wirusy satelitarne oraz (czasem tak nazywane) defektywne wirusy interferujące. 1 z tych 2 sposobów uwzględnienia ich (czy to wliczając do wirusów, czy to wymienić jako nieuwzględnione obok wiroidów, prionów itp.) myślę, że będzie rozsądny, a także przydatny dla czytających.
Dziękuję :)

AD

Dnia 26 lipca 2015 0:35 Adrian Drynda kylie1@o2.pl napisał(a):

Witam serdecznie :)

Muszę na wstępie wspomnieć, że jestem przeogromnie zadowolony, że trafiłem na Pana publikację. Od lat interesuję się tematem i przyznam, że w szkole uczono mnie klasyfikacji jeszcze w stylu 5 królestw. Coraz szybciej zachodzące zmiany w taksonomii spowodowały, że nie byłem w stanie się w tym wszystkim połapać, a polskojęzycznego źródła, które opisywałoby te wszystkie zmiany nie mogłem w żaden sposób znaleźć. Aż w końcu udało mi się trafić na Pana publikację – idealne zestawienie w jaki sposób podział się zmieniał (co dokąd powędrowało itp.), jest także o wirusach, dobrze znanych wiroidach, prionach, ale także o kontrowersyjnych i dotąd nierozstrzygniętych nanobów i nanobakterii.
Jeśli można, chciałbym tylko zasugerować, a także poprosić bardzo Pana o drobne uzupełnienie w publikacji terminów (myślę, że będą one przydatne dla wielu osób czytających publikację, gdyż wiem to po sobie:), a jedynie ich mi tutaj brakuje – myślę, że w miejscu, gdzie wymienia Pan wiroidy, priony itp. warto byłoby dopisać o strukturach zależnych od innych wirusów (wirusów pomocniczych), tj. tzw. wirusach satelitarnych oraz tzw. defektywnych cząsteczkach interferujących, z których obie wymagają do replikacji wirusa pomocniczego, są więc pewną specyficzną dodatkową strukturą. W dodatku, niemal nieopisaną w polskich publikacjach. Sądzę więc, że napomknięcie o nich w Pana publikacji, choćby na zasadzie wtrącenia jak o prionach, będzie bardzo użyteczne i zainteresowana osoba, która natrafi na tę kwestię będzie miała szansę poznać te terminy i dalej szukać (ja miałem tak z nanobami :).
Czy mógłbym więc Pana prosić o zamieszczenie choćby luźnego napomknięcia o tych dwóch strukturach?, które również z organizmami pewien (podobny do wiroidów czy prionów) związek mają
Pozwolę sobie również przy okazji bardzo podziękować za tę publikację. Jest mi ona niezwykle pomocna (co prawda w zakresie stricte hobbystycznym:), ale no wręcz zbawienna!
Z poważaniem i ogromnym podziękowaniem,

AD

Nie znaleziono wirusów w tej wiadomości.
Sprawdzone przez AVG – www.avg.com
Wersja: 2015.0.6081 / Baza danych wirusów: 4392/10323 – Data wydania: 2015–07–28

Szanowny Panie Adrianie!

Nie ma najmniejszego problemu w tym, że przekazuje mi Pan uwagi (za które serdecznie dziękuję) w formie rozproszonej; poczta, która do mnie przychodzi, jest segregowana i trafia do odpowiednich przegródek, dlatego proszę być pewnym, że żadna z tych Pańskich uwag nie zaginie. Kłopot polega jednak na czymś całkiem innym. Otóż są wakacje, a ja mam dodatkowo imprezę w rodzinie – ślub córki, która w dodatku mieszka na stałe za granicą. I naprawdę nie mam na razie w głowie ani sztucznego życia, ani satelitów…

Myślę, że jak się zakończy cały ten szał wakacyjny, i w dodatku jeśli uda mi się to wszystko przeżyć, i wrócić w jednym kawałku do domu, to przyjrzę się problemowi. Jednak zwracam już teraz uwagę, że nadmierne zagłębianie się w temat, który dla Pana okazuje się taki ciekawy, oznaczałoby odejście od tematu artykułu. Zauważyłem przecież, że „nie wiadomo, co zrobić z wirusami, które trudno uznać za żywe, jednak warto docenić ich specyficzną formę organizacji”. W zasadzie wyraziłem tu swoją opinię: wirusy nie są żywe. Gdyby sądzić inaczej, życia nie można by w ogóle zdefiniować – a może ma Pan jakiś pomysł, jak to zrobić?

O wirusach mówi się w kontekście klasyfikacji istot przede wszystkim z uwagi na ich specyficzną organizację. W pewnym sensie można więc uznać je za organizmy (jednak raczej nie za organizmy żywe – wirusy nie mają własnego metabolizmu, a to moim zdaniem sprawę przesądza, jest zupełnie innym problemem, że nie do końca wiadomo, co powinno się uważać za metabolizm). To, że o nich piszę, wynika głównie z faktu, że pewni autorzy włączają wirusy do swoich klasyfikacji biologicznych.

Jednak te uwagi nie odnoszą się już do wiroidów, prionów czy innych tego rodzaju „struktur”. W podręcznikach biologii omawia się je na takiej samej zasadzie, jak powiedzmy organelle komórkowe, a nawet jak biologiczne makrocząsteczki. I chyba słusznie, bo jeśli np. priony uznalibyśmy za organizmy (a tym bardziej za żywe organizmy!), to może każda cząsteczka powinna zostać uznana za organizm? Takie pytanie na pewno powinno zostać postawione w stosunku do plazmidów (które raczej nie uznaje się ani za organizmy, ani za żywe). Dlatego lepiej jest mówić o prionach (i innych podobnych) jako o strukturach, a nie organizmach. Konsekwentnie trudno omawiać je przy okazji klasyfikacji istot żywych…

A co do potencjalnie sztucznego życia… Istnieją ludzie, którzy życie próbują definiować w oderwaniu od metabolizmu (pewnie dlatego, by za żywe uznać wirusy, co moim zdaniem jest drogą prowadzącą na manowce). Dochodzimy wówczas do absurdu, i za żywe zaczynamy uważać na przykład twory wygenerowane przy pomocy komputerów. Zresztą jest to oczywistym skutkiem rezygnacji z jasnych kryteriów życia, takich właśnie jak przemiana materii. Mniejszym absurdem (ale jednak wciąż absurdem) jest uznanie za żywe robotów. Czy roboty, a zwłaszcza czy struktury wygenerowane przez komputery, też należy uwzględnić w klasyfikacji istot żywych?

Pozostaje ostatnia kwestia dotycząca już tylko wirusów i tworów do nich zbliżonych. O ile archeany, bakterie i eukarionty rozpatrywać można w kontekście filogenetycznym (np. zakładając monofiletyczny charakter każdej z tych grup), o tyle trudno doprawdy mówić o filogenezie wirusów (wraz ze strukturami podobnymi) jako całości. O wiele bardziej kuszącą hipotezą jest ta, która zakłada różnorakie i niezależne od siebie pochodzenie różnych grup wirusów. Jeśli więc z góry zakładamy ich polifiletyczny charakter, to błędem byłoby w ogóle mówienie o nich jako o 4. domenie organizmów (a tym bardziej o 4. domenie życia). Wiem oczywiście, że tak właśnie robią niektórzy, ale po pierwsze nie jest to stanowisko powszechne, a po drugie moim zadaniem niszczy ono podstawy klasyfikacji w ogóle, i dlatego powinno się go unikać. Mam nadzieję, że moda na włączanie wirusów wprost do klasyfikacji biologicznej przeminie tak samo, jak niegdysiejsza moda na włączanie skał i minerałów do klasyfikacji „jestestw”.

Jak stwierdziłem wyżej, przyjrzę się jednak problemowi w odpowiednim czasie, i nie wykluczone, że napiszę osobny artykuł poświęcony zagadnieniom, o których nadmieniłem wyżej. Wtedy na pewno napomknę coś i o satelitach czy innych podobnie egzotycznych tworach – natomiast wolałbym unikać rozwijania tego tematu w artykule nt. klasyfikacji istot żywych. To, że w ogóle znalazły się w nim wzmianki o wiroidach i prionach, ma zaś przyczynę czysto praktyczną: wspominają o nich także podręczniki biologii do szkoły średniej. O nanobach czy nanobakteriach natomiast ma okazję usłyszeć każdy, kto w zestawie programów swojego telewizora ma NG czy Discovery. Inne struktury „parażywe” są mniej znane, co zresztą sam Pan zauważył.

No nic… myślę, że mniej więcej naświetliłem stan rzeczy. Proszę więc być cierpliwym, a całkiem możliwe, że doczeka się Pan bardziej konkretnych reakcji z mojej strony. Ale to gdzieś dopiero za miesiąc…

Tymczasem pozdrawiam

Grzegorz Jagodziński

W dniu 2015–07–26 o 16:40, Adrian Drynda pisze:

> Wielce Szanowny Panie Grzegorzu,

> mając nadzieję, że jeszcze moja korespondencja nie została odczytana, chciałbym uporządkować to, co w niej zawarte. Proszę mi wybaczyć, że było to tak chaotyczne i rozdzielone, jest to absolutnie moja wina, proszę tego nie traktować jako brak kultury z mojej strony. Po prostu nieumiejętnie do tego podszedłem. Przepraszam za to :)

> Otóż, skoro napisano o (hipotetycznych/rzekomych wciąż, gdyż z punktu widzenia biologii jeszcze będących nierozstrzygniętym problemem) nanobach i nanobakteriach, warto moim zdaniem dodać również hipotetyczne/potencjalne „sztuczne życie”, które gdyby się pojawiło, zgodnie z wieloma klasyfikacjami – podobnie jak wirusy czy wiroidy – byłoby traktowane jako życie. Przy okazji, warto pamiętać, że coraz częściej także wirusoidy zaczynają być wraz z wirusami traktowane jako 4. domena ewolucyjna organizmów i dzielone na rodziny (Pospiviroidae oraz Avsunvirioidae).

> Również przy wymienieniu takich struktur jak wiroidy czy priony, warto napomknąć moim zdaniem o satelitach (jest to pojęcie nieco szersze, bo obejmujące nie tylko tzw. wirusy satelitarne, ale i tzw. satelitarne kwasy nukleinowe, do których zaliczają się m.in. tzw. wirusoidy), które wraz z wiroidami oraz prionami są zaliczane do tzw. czynników subwirusowych, oraz o tzw. defektywnych cząsteczkach interferujących, które jako pewne specyficzne struktury organiczne zależne od wirusów podobnie jak satelity wymagają pomocy innego wirusa (pomocniczego) do replikacji.

> Myślę, że choć luźne napomknięcie tych kwestii (potencjalne sztuczne życie, satelity i DIPy) będzie uzupełnieniem Pana publikacji oraz informacją, mogącą być przydatną dla czytelników, którzy zechcą dalej szukać. :)

> Bardzo jeszcze raz przepraszam za 4-mailową formę, mój błąd, tu postarałem się jednak zebrać to w całość i dziękuję za odczytanie maila. Czy można prosić o uwzględnienie tych 2 (w zasadzie 3) zagadnień w artykule „Klasyfikacja istot żywych” Pana autorstwa?

> Z poważaniem i uznaniem,

> AD

> Dnia 26 lipca 2015 12:52 Adrian Drynda kylie1@o2.pl napisał(a):

> Jeszcze (przepraszam, że tak podzielone, ale zapomniałem uwzględnić to wcześniej) – jeśli można prosić o zawarcie również tekście napomknięcia o hipotetycznym (potencjalnym) sztucznym życiu (które co prawda jeszcze nie istnieje, jest w fazie hipotetyczności, jednak w wielu opracowaniach padają argumenty, że byłoby ono podobnie żywe jak wirusy i wiroidy). Myślę, że również przydatne czytelnikom będzie napomknięcie, iż próby jego stworzenia istnieją (czytelnik będzie mógł wtedy poszukać większej ilości informacji w tym temacie). Proszę mi wybaczyć aż 3 maile, jednak chciałem te 2 wątki zawrzeć.

> Jeszcze raz dziękuję za świetną, przydatną publikację, prosząc o uwzględnienie tych 2 (satelity+defektywne cząstki oraz hipotetyczne sztuczne życie) w tekście, choćby w formie napomknięcia. :)

> Pozdrawiam jeszcze raz.

> AD

> Dnia 26 lipca 2015 12:27 Adrian Drynda kylie1@o2.pl napisał(a):

> Jeszcze pozwolę sobie tylko uzupełnić – bardzo możliwe, że rozsądnym byłoby po prostu przy wirusach dopisać, że obejmują także satelity i defektywne cząstki interferujące, gdyż są to przecież wirusy satelitarne oraz (czasem tak nazywane) defektywne wirusy interferujące. 1 z tych 2 sposobów uwzględnienia ich (czy to wliczając do wirusów, czy to wymienić jako nieuwzględnione obok wiroidów, prionów itp.) myślę, że będzie rozsądny, a także przydatny dla czytających.
> Dziękuję :)

> AD

> Dnia 26 lipca 2015 0:35 Adrian Drynda kylie1@o2.pl napisał(a):

> Witam serdecznie :)

> Muszę na wstępie wspomnieć, że jestem przeogromnie zadowolony, że trafiłem na Pana publikację. Od lat interesuję się tematem i przyznam, że w szkole uczono mnie klasyfikacji jeszcze w stylu 5 królestw. Coraz szybciej zachodzące zmiany w taksonomii spowodowały, że nie byłem w stanie się w tym wszystkim połapać, a polskojęzycznego źródła, które opisywałoby te wszystkie zmiany nie mogłem w żaden sposób znaleźć. Aż w końcu udało mi się trafić na Pana publikację – idealne zestawienie w jaki sposób podział się zmieniał (co dokąd powędrowało itp.), jest także o wirusach, dobrze znanych wiroidach, prionach, ale także o kontrowersyjnych i dotąd nierozstrzygniętych nanobów i nanobakterii.
> Jeśli można, chciałbym tylko zasugerować, a także poprosić bardzo Pana o drobne uzupełnienie w publikacji terminów (myślę, że będą one przydatne dla wielu osób czytających publikację, gdyż wiem to po sobie:), a jedynie ich mi tutaj brakuje – myślę, że w miejscu, gdzie wymienia Pan wiroidy, priony itp. warto byłoby dopisać o strukturach zależnych od innych wirusów (wirusów pomocniczych), tj. tzw. wirusach satelitarnych oraz tzw. defektywnych cząsteczkach interferujących, z których obie wymagają do replikacji wirusa pomocniczego, są więc pewną specyficzną dodatkową strukturą. W dodatku, niemal nieopisaną w polskich publikacjach. Sądzę więc, że napomknięcie o nich w Pana publikacji, choćby na zasadzie wtrącenia jak o prionach, będzie bardzo użyteczne i zainteresowana osoba, która natrafi na tę kwestię będzie miała szansę poznać te terminy i dalej szukać (ja miałem tak z nanobami :).
> Czy mógłbym więc Pana prosić o zamieszczenie choćby luźnego napomknięcia o tych dwóch strukturach?, które również z organizmami pewien (podobny do wiroidów czy prionów) związek mają
> Pozwolę sobie również przy okazji bardzo podziękować za tę publikację. Jest mi ona niezwykle pomocna (co prawda w zakresie stricte hobbystycznym:), ale no wręcz zbawienna!
> Z poważaniem i ogromnym podziękowaniem,

> AD

> Nie znaleziono wirusów w tej wiadomości.
> Sprawdzone przez AVG – www.avg.com
> Wersja: 2015.0.6081 / Baza danych wirusów: 4392/10323 – Data wydania: 2015–07–28

A virus is a biological agent that reproduces inside the cells of living hosts. When infected by a virus, a host cell is forced to produce many thousands of identical copies of the original virus, at an extraordinary rate. Unlike most living things, viruses do not have cells that divide; new viruses are assembled in the infected host cell. But unlike still simpler infectious agents, viruses contain genes, which gives them the ability to mutate and evolve. Over 5,000 species of viruses have been discovered.[1]

The origins of viruses are unclear: some may have evolved from plasmids-pieces of DNA that can move between cells-while others may have evolved from bacteria. A virus consists of two or three parts: genes, made from either DNA or RNA, long molecules that carry genetic information; a protein coat that protects the genes; and in some viruses, an envelope of fat that surrounds and protects them when they are not contained within a host cell. Viruses vary in shape from the simple helical and icosahedral to more complex structures. Viruses range in size from 20 to 300 nanometres; it would take 30,000 to 750,000 of them, side by side, to stretch to 1 centimetre (0.39 in).

In addition to viruses, structures such as cosmids, satellites, viriods, fosmids, prions, phagemids, and transposons may also be considered non-cellular life

Szanowny Panie Adrianie!

Widzę, że temat, z którym zwrócił się Pan do mnie, stał się dla Pana chyba czymś w rodzaju obsesji. Proszę nie traktować tego jako przytyku – jako zawodowy nauczyciel doceniam, gdy ktoś dąży do jakiegoś celu, ogarnięty pasją. Tak rzadkie to dziś, a przecież o niebo lepsze od uczestniczenia w tzw. imprezach (które tak naprawdę są bardzo często wyzutymi popijawami rozwydrzonej młodzieży). Gdyby więcej ludzi oddawałoby się takim namiętnościom jak zapał do zdobywania wiedzy, mniej byłoby wokół nas nieszczęść…

W związku z tym spytam, czy myślał Pan o tym, by samodzielnie coś stworzyć i podzielić się tym z innymi. Internet jest na to wystarczająco pojemny, a przy tym dość przyjazny dla każdego, kto ma prawdziwą ochotę, by coś opublikować. Można założyć własną witrynę, można publikować na przykład na portalach typu eioba.pl, można też stworzyć nieco bardziej ambitny internetowy pamiętnik, zwany blogiem.

Chodzi o to, że powstała sytuacja dość szczególna: Pan oczekuje, że ja napiszę w moim artykule coś, do czego niespecjalnie jestem przekonany, za to Pan koniecznie chciałby to przeczytać. Przyzna Pan chyba, że jest to dość mało komfortowe? I dla Pana, i dla mnie.

Próbowałem już Panu wyjaśnić mój punkt widzenia, ale chyba zrobiłem to nie do końca jasno. Dlatego więc powtórzę i objaśnię rzecz nieco dokładniej.

Otóż moim skromnym zdaniem wirusy i wszystkie inne formy, o których Pan pisze, nie można nazywać żywymi, a w szczególności bardzo kłopotliwe jest bezpośrednie umieszczanie ich w systematyce żywych organizmów. Istnieją po temu dwa powody. Pierwszym jest fakt, że stworzenie takiej definicji życia, która za żywe uznawałaby wirusy, wiroidy, a może i priony, a nie uznawałaby na przykład plazmidów, wydaje mi się niezwykle trudne. Co więcej, taka definicja byłaby bardzo mało użyteczna.

Może więc zamiast wielokrotnego doprecyzowywania tego, co widziałby Pan w moim artykule, zastanowi się Pan nad postawionym tu problemem? Jeśli chodzi o mnie, myślę, że łatwiej jest postawić granicę życia między bakteriami a wirusami, pozostawiając te drugie po stronie „nieżywe”. Absolutnym nonsensem jest przy tym „definicja” życia dyskutowana u nas np. przez Dzika w jego słynnym podręczniku (który zresztą mam ochotę negatywnie zrecenzować i właśnie nad tym pracuję), według której za żywe należy uznać struktury zdolne do ewolucji. Owa „definicja” abstrahuje bowiem zupełnie od faktu, że organizmy nie ewoluują – ewolucji podlegają dopiero gatunki! Skoro organizmy bywają żywe, ale nie ewoluują, to i ewolucja nie może być kryterium życia. A w każdym razie skłonność organizmów do ulegania zmianom w kolejnych pokoleniach trzeba by całkiem przeformułować – i zacząć raczej właśnie od tych kolejnych pokoleń. Zdolność do wzrostu i rozmnażania przecież też nie może być uznana za kryterium życia, bo gdyby tak było, to robotnica mrówki byłaby martwa tylko dlatego, że nie ma szans się rozmnożyć (to samo można powiedzieć o mule, lub, co jeszcze bardziej z pozoru zaskakujące, o księdzu katolickim – ale to już tylko taka luźna impresja). Skoro zaś mogą istnieć organizmy żywe niezdolne do rozmnażania, to tym bardziej nie mogą być one zdolne do zmian, a więc i do swoiście rozumianej ewolucji.

W definicji życia powinny znaleźć się tylko kryteria obligatoryjne, a nie jakieś niejasne lub absurdalne sformułowania, bo one nie ułatwiają nam dyskusji na przykład nad wirusami. Nie powinno być więc odniesień do ewolucji ani nawet do rozmnażania, chyba, że uda się te zjawiska przeformułować tak, by stworzyć z nich cechy, które posiada każdy żywy organizm. Dla mnie podstawą do dyskusji nad definicją życia byłyby kryteria obligatoryjne Gántiego, zreferowane nie do końca poprawnie w Wikipedii: https://pl.wikipedia.org/wiki/%C5%BBycie#Cechy_konieczne, stąd lepiej byłoby dyskutować nad ich sformułowaniem zawartym w książce tego autora (np. punkt pierwszy w oryginale mówi, że układ żywy jest inherentną całością, tj. funkcjonuje tylko jako całość, ale żywa nie jest żadna z jego części rozpatrywana osobno – jak widać, autor wiki kompletnie to przeinaczył). Zwracam uwagę na cechy 2 i 5: konieczność zachodzenia wewnątrz układu żywego jakichś procesów, określanych ogólnie mianem metabolizmu, a także kontrola układu żywego nad tymi procesami. Wirusy tych kryteriów nie spełniają, co eliminuje je z grona istot żywych.

Ma Pan prawo oczywiście nie zgadzać się z taką definicją, ale wówczas proszę wypisać sobie na kartce przykłady tego, co według Pana jest żywe, oraz tego, co nie jest żywe (proponuję uwzględnić na przykład między innymi robotnicę mrówki, niesporczaka w stanie anabiozy, riketsję, wirusa, chloroplast lub mitochondrium, program komputerowy przedstawiający tzw. sztuczne życie – riketsję wymieniłem dlatego, że jej środowiskiem życia są żywe komórki, poza którymi nie jest w stanie funkcjonować, a zwłaszcza rozmnażać się). Bardzo chętnie zapoznam się z rezultatami Pańskich dociekań. I zapewniam, że po pierwsze będzie to z większym pożytkiem niż monitowanie mnie, co mam zmienić w swoich artykułach, a po drugie otworzy drogę do ciekawej dyskusji. Ba, może nawet uda się Panu przekonać mnie do zmiany stanowiska!

Jak wyżej zaznaczyłem, jest jeszcze jeden powód, dla którego wirusy wolałbym wykluczyć z systemu istot żywych. Pisałem już o tym, ale napiszę raz jeszcze. W założeniu jednostki systematyczne mają odzwierciedlać historię rodową i rzeczywiste pokrewieństwa między organizmami. Wirusy (i podobne twory) i w tym punkcie stanowią problem, bo istnieją poważne obawy, że nie stanowią one grupy naturalnej, a nawet że powstawały wielokrotnie i to w różny sposób. Być może niektóre ich „gatunki” stanowią produkt ewolucji pierwszych form życia, które pierwotnie nie były same zdolne do przeprowadzania procesów metabolicznych i czerpały z ówczesnego środowiska. Z czasem jednak organizmy „indywidualizowały” się coraz mocniej, a te, które „nie zdążyły”, zostały zmuszone do swoistego rodzaju pasożytnictwa. Podejrzewa się zwłaszcza, że wiroidy mogą wywodzić się ze struktur funkcjonujących w „świecie RNA”, który poprzedzał właściwy świat organizmów żywych w historii naszej planety.

Część wirusów mogła powstać poprzez stopniowe upraszczanie budowy i zdolności do funkcjonowania organizmów żywych w rodzaju dzisiejszych riketsji czy chlamydii (przy okazji, obie te grupy uważano kiedyś za blisko spokrewnione, dziś natomiast wiemy, że znajdują się one na zupełnie innych konarach drzewa rodowego prokariontów). Tą drogą miały powstać zwłaszcza „gigawirusy” odkryte ostatnio przez francuskich uczonych z Marsylii i okrzyczanych przez nich czwartą domeną życia (odrębną od wszystkich innych wirusów). Ich DNA zawiera (niefunkcjonujące) geny kodujące np. enzymy uczestniczące w translacji, co może być pozostałością po metabolizujących przodkach.

Wreszcie część wirusów mogła powstać z plazmidów czy transpozonów, które uległy autonomizacji i „nauczyły się” wędrować samodzielnie od komórki do komórki. W tym kontekście ważkie staje się też pytanie o pochodzenie samych plazmidów i transpozonów, ale to także problem, którym mógłby się Pan zająć.

Osobiście uważam, że w powstaniu wirusów i tworów podobnych brał udział każdy w powyżej wymienionych mechanizmów, stąd pytanie o to, która z teorii pochodzenia wirusów jest prawdziwa, jest źle sformułowane, bo te teorie nie muszą się wykluczać. Ale skoro tak, to pojęcie „wirusy” jest tak samo sztuczne jak na przykład pojęcie „porosty”. Skoro z systematyki zniknęły porosty, nie powinno się do niej włączać wirusów.

Nie może być raczej mowy o parafiletyzmie wirusów. Jest to grupa ewidentnie już nawet nie polifiletyczna, ale wręcz sztuczna, skoro łączy twory powstałe z żywych organizmów z tworami powstałymi w wyniki autonomizacji ich fragmentów. Klasyfikować je można i należy, ale na takiej samej zasadzie, jak klasyfikuje się skały czy minerały. Przecież na podobnej zasadzie moglibyśmy klasyfikować plazmidy, i miałoby to równie mało wspólnego z tradycyjną systematyką biologiczną.

W artykule /pl/system.html wspominam co prawda o wirusach, ale tylko dlatego, że referuję to, co zostało w tej sprawie opublikowane. Tuż nad tabelą wspominam jeszcze cztery rodzaje tworów: nanobakterie, nanoby, wiroidy i priony, nie precyzując zresztą, czym te twory są. Nie widzę naprawdę potrzeby, by tę listę rozszerzać, i zaraz wyjaśnię, dlaczego.

Nanobakterie uważa się obecnie za artefakty powstałe w wyniku procesów nieorganicznych, nie mają one więc żadnego związku z życiem opartym na węglu, wodorze, tlenie i azocie. Co do nanobów, sytuacja jest niejasna i wymaga dalszych badań, i właśnie dlatego brak ich w zestawieniu. Wiroidy i priony są pojedynczymi makrocząsteczkami (odpowiednio RNA i białka), stąd też dyskutowanie nad ich charakterem jako tworów żywych wydaje mi się naprawdę przekraczać granicę absurdu.

Natomiast co do satelitów i defektywnych cząsteczkach interferujących to właściwie można ze spokojnym sumieniem włączyć je do klas wirusów i wiroidów, co też zresztą się czyni. Rozmawiałem na ten temat z córką, która pracuje na uniwersytecie w Montpellier i zajmuje się biotechnologią i inżynierią genetyczną, więc z natury rzeczy łatwiej jej się zetknąć z problematyką tych tworów niż mnie, skromnemu biologowi. Zwracam uwagę, że w polskiej literaturze zwykle zamiast „satelity” używa się nazwy „wirusy satelitarne”, co tym bardziej usprawiedliwia moje stanowisko. W obowiązującej dziś klasyfikacji wirusów tzw. satelity wymienia się wprost w odpowiedniej klasie tych tworów, co nawet przy zachowaniu ich specjalnej nazwy i tak wskazuje jasno na to, że są to szczególne wirusy.

Mam wręcz wrażenie, że w sprawie tzw. tworów subwiralnych nie ma jeszcze stosownego konsensusu w nauce, stąd właśnie problemy ze zdobyciem rzetelnych informacji. Ogólnie rzecz biorąc, wirus składa się z kapsydu i kwasu nukleinowego (czasami też z otoczki), zaś wiroid to cząsteczka kwasu nukleinowego (na ogół RNA, ale nie wiem, czy tego paradygmatu przypadkiem już nie przełamano) bez kapsydu. Wirusy satelitarne wyglądają jak każde inne wirusy (czyli też mają kapsyd i kwas nukleinowy), ale z takich czy innych powodów (właśnie, z jakich dokładnie?) nie są w stanie same dokonać inwazji na komórkę żywiciela, i potrzebują do tego „pomocy” innego wirusa. Nie za bardzo jest dla mnie jasna różnica między wirusem satelitarnym a wirofagiem – odnoszę wrażenie, że ten ostatni termin ukuli badacze, którzy dbali po prostu o to, by przejść do podręczników. Wirofagi to wirusy pasożytujące na wirusach – ale na czym miałoby to pasożytnictwo polegać, nie wiem. Chyba jednak dokładnie na tym samym, na czym zależność wirusów satelitarnych od wirusów pomocniczych. Jak będę miał chwilę czasu, spróbuję wgłębić się w to zagadnienie. Niezależnie jednak od wyniku, zarówno satelity, jak i wirofagi (o ile w ogóle są to twory odrębne) są po prostu szczególnymi rodzajami wirusów. Nie ma więc potrzeby rozszerzać podanej przeze mnie listy wyjątków, zresztą obie te grupy jak wspomniałem klasyfikuje się w obrębie wirusów, a zatem nie stanowią one żadnego wyjątku (znajdują się wśród grup wymienionych w tabeli).

Podobny kłopot nazewniczy istnieje z defektywnymi cząsteczkami interferującymi (DCI), a także takimi tworami, jak wirusoidy (nie mylić z wiroidami, choć pojęcia te są zależne). Okazuje się bowiem, że owe DCI to po prostu wiroidy niezdolne do samodzielnego ataku na komórkę – czyli cząsteczki kwasów nukleinowych, które do namnożenia potrzebują nie tylko komórki, ale jeszcze wirusa (lub wiroida?). Dotarłem zresztą do informacji, że wśród takich cząsteczek występuje zwykłe, jednoniciowe kodujące RNA, i wówczas właśnie mówi się o wirusoidach (których stosunek do wiroidów byłby taki sam jak satelitów do wirusów). Istnieją jednak także podobnego rodzaju cząsteczki o innej budowie (dwuniciowego RNA, albo też DNA), które także działają w podobny sposób. Jeśli moje obecne rozumienie problemu (po pobieżnym zapoznaniu się z kilkoma artykułami) jest słuszne, to wirusoidy są szczególnym rodzajem DCI, a wszystkie DCI są szczególnym rodzajem szeroko rozumianych wiroidów (bez wymogu, że musiałyby to być cząsteczki jednoniciowego kodującego RNA). A skoro tak, nie ma powodu, by cokolwiek dopisywać do mojego artykułu, bo przecież o wiroidach wspomniałem. Jedyne, o czym można by wspomnieć, jest fakt, że wiroidy (a więc także DCI) czasem włącza się wprost do wirusów, i poszczególne ich klasy omawia przy poszczególnych klasach tych ostatnich (uważam, że to całkiem sensowne). Gdyby uznać wirusy za żywe, niekiedy atrybut taki przypisalibyśmy pojedynczym cząsteczkom… Dla mnie to jest niedorzeczne, stąd moje nieprzejednane stanowisko. A przy okazji, jeśli wiroidy zalicza się czasem do wirusów, to może powinienem usunąć je z listy wyjątków? Zamiast dopisywać do niej kolejne grupy zgodnie z Pana życzeniem, powinienem raczej ją uszczuplić… przynajmniej o jedną grupę.

Na koniec dla porządku tylko: wspomniałem o nieumieszczeniu w klasyfikacji prionów, a to dlatego, że stanowią one także cząsteczki, i doprawdy trudno byłoby je uznać za organizmy.

Zdaję sobie sprawę oczywiście, że nie wszyscy tak uważają, i polecam na przykład artykuł (po ang.) http://www.wisegeek.com/what-is-non-cellular-life.htm. Wśród niekomórkowych form życia wymieniono tam – uwaga! – wirusy, kosmidy, satelity, wiroidy (literówka w nazwie!), fosmidy, priony, fagemidy (nie mam pojęcia, co to jest, ale postaram się dowiedzieć) i transpozony (zwane u nas często genami skaczącymi, polecam np. http://www.biotechnolog.pl/transpozony-skaczace-geny-wspomagajace-ewolucje). No cóż… skoro formami życia miałyby być cząsteczki białek albo pojedyncze geny…

Pańską listę życzeń właściwie więc spełniłem, bo twory, o które Pan apeluje, włącza się (lub przynajmniej można włączyć) do grup przeze mnie wymienionych. Pozostał więc właściwie tylko punkt ostatni, dotyczący potencjalne sztuczne życie. I tu również niestety zmuszony jestem zaprotestować, a to z dwóch powodów.

Po pierwsze, jeśli ma Pan na myśli życie niekomórkowe, to wie Pan, jakie jest moje stanowisko. Po prostu uznaję to pojęcie za nie do końca słuszne. A argument podany w artykule na wisegeek do mnie nie przemawia: jak to, “the fact that some viruses are capable of producing proteins”? Przecież KAŻDY wirus (nie wiroid) jest w pewnym sensie zdolny do produkcji białek! Gdyby tak nie było, skąd wziąłby się jego kapsyd? A poza tym, czy to rzeczywiście wirus jest zdolny? Czy wirus ma mRNA, rybosomy, cały niezbędny aparat enzymatyczny? Czy też może zaprzęga do tej pracy komórkę? Może czegoś nie doczytałem, ale twory w rodzaju Mimivirus mają jedynie o wiele więcej genów niż normalne wirusy, ale i tak nie są w stanie same zrobić z nich żadnego użytku, a więc pod tym względem nie ma żadnej różnicy między nimi a innymi wirusami (a artykuł jest zwykłą kaczką dziennikarską – ktoś czegoś nie doczytał, coś przeinaczył, i od razu zrobił aferę).

Według tego, co udało mi się dowiedzieć (większość znajdzie Pan na angielskiej wiki pod hasłem Mimivirus – polska wersja jest rozpaczliwie żałosna i nie podaje żadnych informacji), Mimivirus dysponuje nie tylko genami pewnych białek, ale także przygotowanymi, gotowymi transkryptami (czyli obok DNA zawiera też RNA! – i to jest niezwykłe, a nie to, że wirus zawiera geny białek), które osobno ulegają translacji i to zanim w ogóle dojdzie do namnożenia całego genomu wirusa (“Several mRNA transcripts can be recovered from purified virions”). Mało to, właśnie powstałe z tych transkryptów białka dopiero stymulują namnażanie wirusa. Jednak wciąż proces ich wytworzenia wymaga dostania się wirusa do komórki gospodarza i skorzystania z jej aparatu translacji. Mamy więc do czynienia z wirusem o tyle niezwykłym, że zawierającym dwa typy kwasów nukleinowych (znane są jednak także inne takie wirusy). Czy to jednak czyni z niego żywy organizm? Nie jest to wciąż kapsuła zbudowana z chemicznych cząsteczek, samodzielnie niezdolna do żadnego działania?

Wracając jednak do tematu: czy o takim sztucznym życiu Pan myśli? Powtarzam, dla mnie nie jest to jeszcze życie, tak samo jak życiem nie jest całkowicie sztucznie skonstruowany chromosom bakteryjny, który wprowadza się do komórki jak plazmid, i który zmienia właściwości bakterii. Takie cuda robią już biotechnolodzy, o czym świetnie wie moja córka, ale to tylko tak na marginesie. Dla mnie żywa jest wciąż bakteria, a wprowadzona cząsteczka nie jest żywa, podobnie jak wprowadzony program nie jest jeszcze komputerem. Nie jest to więc żadne sztuczne życie, ale raczej manipulacja przy tym, co jest żywe. Po prostu inżynieria genetyczna. Ingerencja w życie, ale nie jego tworzenie de novo.

Po drugie, jeśli ma Pan na myśli życie komórkowe, to także moja odpowiedź na Pański postulat jest negatywna. Jestem przekonany, że kiedyś zgromadzimy tak wielką wiedzę, że uda nam się zaprojektować i stworzyć od podstaw twór, który nawet tacy sceptycy jak ja nazwą żywym organizmem. Będzie on w stanie przetwarzać materię i energię, sprawując kontrolę nad tym procesem, oraz powielić się tak, jak to robią autentyczne żywe organizmy. O ile nie wykończą nas jacyś religijni fanatycy z ISIS, to pewnie nasza cywilizacja nie zatrzyma się na drodze do wiedzy, bo taka już jest natura człowieka. Póki co jednak takie osiągnięcia pozostają jednak domeną science-fiction, i to bardziej fiction niż science. I dlatego powiem tak: jeśli dowiem się, że ktoś stworzył życie w probówce (życie, a nie jakiegoś wirusa!) , to wówczas pomyślę, co z tym fantem zrobić.

Na podobnej zasadzie nie będę rozważał, do jakiej rubryki tabeli wpisać kosmitów. Oficjalnie przynajmniej takich dotąd nie stwierdzono, a gdy już ich się znajdzie, to wówczas dopiero spróbuje jakoś poklasyfikować. Myślę, że ze sztucznym życiem jest dokładnie tak samo. Najpierw je zróbmy, potem będziemy się martwić.

Proszę zauważyć, że w tabeli są wyłącznie grupy REALNYCH organizmów (plus wirusy, które trudno uznać za organizmy, za to za realne jak najbardziej). Nie ma tam ani jednej grupy potencjalnej. Dlaczego więc miałbym w ogóle wymieniać coś potencjalnego? Gdybym dopisał (gdziekolwiek, do tabeli lub nad nią) sztuczne życie, to dlaczego nie kosmitów, dlaczego nie elfy i leśne duszki? Proszę się nad tym zastanowić na spokojnie…

Chętnie też dowiem się od Pana, jak Pan sobie to sztuczne życie wyobraża, i to w możliwie jak najdrobniejszych szczegółach. Może stworzy Pan artykuł na ten temat? Jeśli Pana interesuje tak bardzo ten temat, to może naprawdę warto!

Ufff… to myślę byłoby na tyle. Skłaniam się więc jak Pan widzi do tego, by nie spełnić żadnego z Pańskich postulatów, i nie wprowadzać zmian do artykułu. W moim pojęciu jest dobrze właśnie tak, jak jest. Jest jednak całkiem inną sprawą, że naprawdę doceniam Pańskie zaangażowanie i pasję (i dlatego namawiam do własnych poszukiwań i do stworzenia własnej publikacji internetowej). Gdy tylko skończę ze sprawami, którymi się obecnie zajmuję, pomyślę o artykule na temat definicji życia. A wówczas z pewnością wykorzystam wszystkie te egzotyczne grupy tworów, o których tu pisałem, choćby tylko po to, by przybliżyć czytelnikom zagadnienia, o których najczęściej można poczytać w pisanych hermetycznym językiem artykułach naukowych (i do tego po angielsku). Jak Pan widzi, sam nie mam tu bynajmniej kompletnej wiedzy, i muszę sporo jeszcze doczytać, nim cokolwiek będę mógł przekazać. Myślę, że jeśli taki artykuł powstanie, zostanie też odpowiednia zlinkowany z tekstem o klasyfikacji istot żywych. Ale właśnie wtedy właśnie będzie dopiero na to odpowiedni czas…

Tymczasem jednak gorąco pozdrawiam, już z Libiąża w Polsce :-) Swoją drogą, tak sobie teraz dopiero myślę, że miałem jednak niesamowitą odwagę, by wybrać się siedemnastoletnim autem (fakt, niezawodnym, ale jednak) w podróż 2000 km w jedną stronę, do obcego kraju, gdzie mówią językiem, który znam jedynie rudymentarnie… Przecież gdyby coś się stało… No ale jakoś szczęśliwie objechałem, jestem cały i zdrowy (auto też), i mogę z przyjemnością wrócić do dawnych rodzajów aktywności.

Rok szkolny za pasem, a ja już jutro mam mieć pierwszego ucznia w tym sezonie na domowych korepetycjach… tak że zmuszony jestem się pożegnać i udać się na spoczynek, żebym przez przypadek nie zaczął dziewczynie, która do mnie ma przyjść, opowiadać o różnicy między wirusami a wiroidami… :-)

Grzegorz Jagodziński

W dniu 2015–08–19 o 22:10, Adrian Drynda pisze:

> Szanowny Panie Grzegorzu!

> Korzystając jeszcze z okazji, chciałbym doprecyzować: przez pojęcie „potencjalne «sztuczne życie»” rozumiem oczywiście hipotetyczne i możliwe do stworzenia w warunkach sztucznych (tj. w laboratorium) tzw. syntetyczne/sztuczne życie.

> Jeszcze raz gorąco pozdrawiam! :)

> AD

> Dnia 2 sierpnia 2015 23:00 Adrian Drynda kylie1@o2.pl napisał(a):

> Szanowny Panie Grzegorzu!
> Ogromnie dziękuję za odpowiedź, zwłaszcza tak wyczerpującą, jestem wręcz zaszczycony. Przepraszam przy tym za zawracanie głowy w czasie wakacyjnym, a tym bardziej w tak ważnym momencie jak ślub córki! :)
> Powiem szczerze, że podzielam przedstawiony w Pana mailu pogląd – choć w ostatnich latach często pojawia się pomysł traktowania wirusów (wraz z wiroidami) jako żywych i wyodrębnienia 4. domeny życia, sugerując że możemy tu mieć wówczas do czynienia z grupą para- lub polifiletyczną, to ja również raczej obstaję przy traktowaniu ich właśnie jako specyficznych form „organizmów” (?), których po prostu skomplikowana struktura i organizacja zasługuje na choćby pewne ich pogrupowanie i uwzględnienie.
> Zgadzam się również w 100%, że artykuł na temat klasyfikacji istot żywych nie powinien zawierać szczegółowego roztrząsania problemu struktur „parażywych” typu priony czy wirusy. Zdecydowanie ma Pan rację, byłoby to niepotrzebne odchodzenie od tematu głównego. A zarazem troszkę mieszanie różnych zakresów informacji. Przyznam szczerze, że gdyby rzeczywiście napisał Pan w przyszłości osobny artykuł o tego typu „strukturach organicznych” jak priony czy satelity, zaczytywałbym się w nim zapewne równie tak dogłębnie jak w przypadku omawianego artykułu. :)
> Mówiąc zupełnie szczerze, gdyby nie Pana artykuł (w końcu polskojęzyczna publikacja, opisująca temat od początku do końca) nie potrafiłbym do końca połapać się co potraktowano jako stramenopile czy alweolaty itp. Więc jeszcze raz serdecznie dziękuję. :)
> Oczywiście tematyka sztucznego życia jest w zasadzie obecnie tematem jedynie hipotetycznym (i to nawet jeśli mowa o maszynach samoreplikujących, ale także stworzonych w warunkach laboratoryjnych „żywych” komórkach), jednak jest to też powiązane z tematem zagadnienie. Często, gdy naukowcy używają definicji życia jako dynamiczne, samoorganizujące się struktury, zdolne do samopowielania się i ewolucji (co np. odbiera status żywych kompletnie nieuzasadnionym programom komputerowym itp.), obejmują tym zakresem sztuczne życie czy wirusy. Jednak (choć przywołuję tę informację) wcale nie utożsamiam się z nią. Jak już na początku wspomniałem, jestem raczej zdania, że wirusy i inne podobne „struktury” należy może i traktować jako organizmy, ale nie do końca jako „żywe” (a raczej z życiem związane).
> Odnosząc się jednak precyzyjniej do mojej propozycji (czy też prośby), chodzi mi bardziej o bardzo luźne napomknięcie tych kwestii. Mianowicie, mam na myśli mniej więcej coś takiego: W zdaniu Nie uwzględniono w niej nanobakterii, nanobów, wiroidów ani prionów, których charakter jako organizmów jest niejasny, kwestionowany lub (w wypadku nanobakterii) w zasadzie odrzucony, chciałbym zaproponować i poprosić o pewne uzupełnienie. Może przedstawię jakiś przykład, żeby precyzyjnie wyrazić, o co mi chodzi. Np. proponuję mniej więcej taką formę: Nie uwzględniono w niej potencjalnego „sztucznego życia”, nanobakterii, nanobów, wiroidów, satelitów, defektywnych cząsteczek interferujących ani prionów, których charakter jako organizmów jest niejasny, kwestionowany lub (w wypadku nanobakterii) w zasadzie odrzucony. Mniej więcej o czymś takim myślałem.
> Uważam, że takie dopełnienie zdania może mieć kilka zalet: po pierwsze będzie uzupełnieniem informacji, a więc jej dopełnieniem (dzięki temu przekrój uwzględnionych danych będzie szerszy i pełny), po drugie może być przydatne dla czytających (którzy widząc napomknięcie o satelitach tak jak prionach czy nanobach mogą dalej szukać informacji z tego zakresu), a jednocześnie nie będzie to odejściem od głównej tematyki (nieuzasadnionym byłoby rozwijanie wątku tych wszystkich „struktur” czy zagadnień w tymże artykule, gdyż – słusznie – prowadziłoby to na manowce :) ), a jedynie krótkim dopełniającym zdanie napomknięciem. Sądzę, że z tych powodów może być to celowe, a zarazem niepowodujące odejścia od tematu, o którym obaj wspomnieliśmy.
> Czy można więc prosić o takie uzupełnienie tego zdania (w mniej więcej podobnej formie; podałem ją, by dobrze wyrazić to, o co mi chodziło)?
> Przy okazji chciałbym Panu życzyć udanego wypoczynku wakacyjnego, a także złożyć serdeczne życzenia Pańskiej córce i wybrankowi Jej serca oraz pogratulować serdecznie Panu. :)
> Pozdrawiam serdecznie,

> AD

> Dnia 28 lipca 2015 11:05 Grzegorz Jagodziński grzegorj@interia.pl napisał(a):

> Szanowny Panie Adrianie!

> Nie ma najmniejszego problemu w tym, że przekazuje mi Pan uwagi (za które serdecznie dziękuję) w formie rozproszonej; poczta, która do mnie przychodzi, jest segregowana i trafia do odpowiednich przegródek, dlatego proszę być pewnym, że żadna z tych Pańskich uwag nie zaginie. Kłopot polega jednak na czymś całkiem innym. Otóż są wakacje, a ja mam dodatkowo imprezę w rodzinie – ślub córki, która w dodatku mieszka na stałe za granicą. I naprawdę nie mam na razie w głowie ani sztucznego życia, ani satelitów…

> Myślę, że jak się zakończy cały ten szał wakacyjny, i w dodatku jeśli uda mi się to wszystko przeżyć, i wrócić w jednym kawałku do domu, to przyjrzę się problemowi. Jednak zwracam już teraz uwagę, że nadmierne zagłębianie się w temat, który dla Pana okazuje się taki ciekawy, oznaczałoby odejście od tematu artykułu. Zauważyłem przecież, że „nie wiadomo, co zrobić z wirusami, które trudno uznać za żywe, jednak warto docenić ich specyficzną formę organizacji”. W zasadzie wyraziłem tu swoją opinię: wirusy nie są żywe. Gdyby sądzić inaczej, życia nie można by w ogóle zdefiniować – a może ma Pan jakiś pomysł, jak to zrobić?

> O wirusach mówi się w kontekście klasyfikacji istot przede wszystkim z uwagi na ich specyficzną organizację. W pewnym sensie można więc uznać je za organizmy (jednak raczej nie za organizmy żywe – wirusy nie mają własnego metabolizmu, a to moim zdaniem sprawę przesądza, jest zupełnie innym problemem, że nie do końca wiadomo, co powinno się uważać za metabolizm). To, że o nich piszę, wynika głównie z faktu, że pewni autorzy włączają wirusy do swoich klasyfikacji biologicznych.

> Jednak te uwagi nie odnoszą się już do wiroidów, prionów czy innych tego rodzaju „struktur”. W podręcznikach biologii omawia się je na takiej samej zasadzie, jak powiedzmy organelle komórkowe, a nawet jak biologiczne makrocząsteczki. I chyba słusznie, bo jeśli np. priony uznalibyśmy za organizmy (a tym bardziej za żywe organizmy!), to może każda cząsteczka powinna zostać uznana za organizm? Takie pytanie na pewno powinno zostać postawione w stosunku do plazmidów (które raczej nie uznaje się ani za organizmy, ani za żywe). Dlatego lepiej jest mówić o prionach (i innych podobnych) jako o strukturach, a nie organizmach. Konsekwentnie trudno omawiać je przy okazji klasyfikacji istot żywych…

> A co do potencjalnie sztucznego życia… Istnieją ludzie, którzy życie próbują definiować w oderwaniu od metabolizmu (pewnie dlatego, by za żywe uznać wirusy, co moim zdaniem jest drogą prowadzącą na manowce). Dochodzimy wówczas do absurdu, i za żywe zaczynamy uważać na przykład twory wygenerowane przy pomocy komputerów. Zresztą jest to oczywistym skutkiem rezygnacji z jasnych kryteriów życia, takich właśnie jak przemiana materii. Mniejszym absurdem (ale jednak wciąż absurdem) jest uznanie za żywe robotów. Czy roboty, a zwłaszcza czy struktury wygenerowane przez komputery, też należy uwzględnić w klasyfikacji istot żywych?

> Pozostaje ostatnia kwestia dotycząca już tylko wirusów i tworów do nich zbliżonych. O ile archeany, bakterie i eukarionty rozpatrywać można w kontekście filogenetycznym (np. zakładając monofiletyczny charakter każdej z tych grup), o tyle trudno doprawdy mówić o filogenezie wirusów (wraz ze strukturami podobnymi) jako całości. O wiele bardziej kuszącą hipotezą jest ta, która zakłada różnorakie i niezależne od siebie pochodzenie różnych grup wirusów. Jeśli więc z góry zakładamy ich polifiletyczny charakter, to błędem byłoby w ogóle mówienie o nich jako o 4. domenie organizmów (a tym bardziej o 4. domenie życia). Wiem oczywiście, że tak właśnie robią niektórzy, ale po pierwsze nie jest to stanowisko powszechne, a po drugie moim zadaniem niszczy ono podstawy klasyfikacji w ogóle, i dlatego powinno się go unikać. Mam nadzieję, że moda na włączanie wirusów wprost do klasyfikacji biologicznej przeminie tak samo, jak niegdysiejsza moda na włączanie skał i minerałów do klasyfikacji „jestestw”.

> Jak stwierdziłem wyżej, przyjrzę się jednak problemowi w odpowiednim czasie, i nie wykluczone, że napiszę osobny artykuł poświęcony zagadnieniom, o których nadmieniłem wyżej. Wtedy na pewno napomknę coś i o satelitach czy innych podobnie egzotycznych tworach – natomiast wolałbym unikać rozwijania tego tematu w artykule nt. klasyfikacji istot żywych. To, że w ogóle znalazły się w nim wzmianki o wiroidach i prionach, ma zaś przyczynę czysto praktyczną: wspominają o nich także podręczniki biologii do szkoły średniej. O nanobach czy nanobakteriach natomiast ma okazję usłyszeć każdy, kto w zestawie programów swojego telewizora ma NG czy Discovery. Inne struktury „parażywe” są mniej znane, co zresztą sam Pan zauważył.

> No nic… myślę, że mniej więcej naświetliłem stan rzeczy. Proszę więc być cierpliwym, a całkiem możliwe, że doczeka się Pan bardziej konkretnych reakcji z mojej strony. Ale to gdzieś dopiero za miesiąc…

> Tymczasem pozdrawiam

> Grzegorz Jagodziński

> W dniu 2015–07–26 o 16:40, Adrian Drynda pisze:

> Wielce Szanowny Panie Grzegorzu,

> mając nadzieję, że jeszcze moja korespondencja nie została odczytana, chciałbym uporządkować to, co w niej zawarte. Proszę mi wybaczyć, że było to tak chaotyczne i rozdzielone, jest to absolutnie moja wina, proszę tego nie traktować jako brak kultury z mojej strony. Po prostu nieumiejętnie do tego podszedłem. Przepraszam za to :)

> Otóż, skoro napisano o (hipotetycznych/rzekomych wciąż, gdyż z punktu widzenia biologii jeszcze będących nierozstrzygniętym problemem) nanobach i nanobakteriach, warto moim zdaniem dodać również hipotetyczne/potencjalne „sztuczne życie”, które gdyby się pojawiło, zgodnie z wieloma klasyfikacjami – podobnie jak wirusy czy wiroidy – byłoby traktowane jako życie. Przy okazji, warto pamiętać, że coraz częściej także wirusoidy zaczynają być wraz z wirusami traktowane jako 4. domena ewolucyjna organizmów i dzielone na rodziny (Pospiviroidae oraz Avsunvirioidae).

> Również przy wymienieniu takich struktur jak wiroidy czy priony, warto napomknąć moim zdaniem o satelitach (jest to pojęcie nieco szersze, bo obejmujące nie tylko tzw. wirusy satelitarne, ale i tzw. satelitarne kwasy nukleinowe, do których zaliczają się m.in. tzw. wirusoidy), które wraz z wiroidami oraz prionami są zaliczane do tzw. czynników subwirusowych, oraz o tzw. defektywnych cząsteczkach interferujących, które jako pewne specyficzne struktury organiczne zależne od wirusów podobnie jak satelity wymagają pomocy innego wirusa (pomocniczego) do replikacji.

> Myślę, że choć luźne napomknięcie tych kwestii (potencjalne sztuczne życie, satelity i DIPy) będzie uzupełnieniem Pana publikacji oraz informacją, mogącą być przydatną dla czytelników, którzy zechcą dalej szukać. :)

> Bardzo jeszcze raz przepraszam za 4-mailową formę, mój błąd, tu postarałem się jednak zebrać to w całość i dziękuję za odczytanie maila. Czy można prosić o uwzględnienie tych 2 (w zasadzie 3) zagadnień w artykule „Klasyfikacja istot żywych” Pana autorstwa?

> Z poważaniem i uznaniem,

> AD

> Dnia 26 lipca 2015 12:52 Adrian Drynda kylie1@o2.pl napisał(a):

> Jeszcze (przepraszam, że tak podzielone, ale zapomniałem uwzględnić to wcześniej) – jeśli można prosić o zawarcie również tekście napomknięcia o hipotetycznym (potencjalnym) sztucznym życiu (które co prawda jeszcze nie istnieje, jest w fazie hipotetyczności, jednak w wielu opracowaniach padają argumenty, że byłoby ono podobnie żywe jak wirusy i wiroidy). Myślę, że również przydatne czytelnikom będzie napomknięcie, iż próby jego stworzenia istnieją (czytelnik będzie mógł wtedy poszukać większej ilości informacji w tym temacie). Proszę mi wybaczyć aż 3 maile, jednak chciałem te 2 wątki zawrzeć.

> Jeszcze raz dziękuję za świetną, przydatną publikację, prosząc o uwzględnienie tych 2 (satelity+defektywne cząstki oraz hipotetyczne sztuczne życie) w tekście, choćby w formie napomknięcia. :)

> Pozdrawiam jeszcze raz.

> AD

> Dnia 26 lipca 2015 12:27 Adrian Drynda kylie1@o2.pl napisał(a):

> Jeszcze pozwolę sobie tylko uzupełnić – bardzo możliwe, że rozsądnym byłoby po prostu przy wirusach dopisać, że obejmują także satelity i defektywne cząstki interferujące, gdyż są to przecież wirusy satelitarne oraz (czasem tak nazywane) defektywne wirusy interferujące. 1 z tych 2 sposobów uwzględnienia ich (czy to wliczając do wirusów, czy to wymienić jako nieuwzględnione obok wiroidów, prionów itp.) myślę, że będzie rozsądny, a także przydatny dla czytających.
> Dziękuję :)

> AD

> Dnia 26 lipca 2015 0:35 Adrian Drynda kylie1@o2.pl napisał(a):

> Witam serdecznie :)

> Muszę na wstępie wspomnieć, że jestem przeogromnie zadowolony, że trafiłem na Pana publikację. Od lat interesuję się tematem i przyznam, że w szkole uczono mnie klasyfikacji jeszcze w stylu 5 królestw. Coraz szybciej zachodzące zmiany w taksonomii spowodowały, że nie byłem w stanie się w tym wszystkim połapać, a polskojęzycznego źródła, które opisywałoby te wszystkie zmiany nie mogłem w żaden sposób znaleźć. Aż w końcu udało mi się trafić na Pana publikację – idealne zestawienie w jaki sposób podział się zmieniał (co dokąd powędrowało itp.), jest także o wirusach, dobrze znanych wiroidach, prionach, ale także o kontrowersyjnych i dotąd nierozstrzygniętych nanobów i nanobakterii.
> Jeśli można, chciałbym tylko zasugerować, a także poprosić bardzo Pana o drobne uzupełnienie w publikacji terminów (myślę, że będą one przydatne dla wielu osób czytających publikację, gdyż wiem to po sobie:), a jedynie ich mi tutaj brakuje – myślę, że w miejscu, gdzie wymienia Pan wiroidy, priony itp. warto byłoby dopisać o strukturach zależnych od innych wirusów (wirusów pomocniczych), tj. tzw. wirusach satelitarnych oraz tzw. defektywnych cząsteczkach interferujących, z których obie wymagają do replikacji wirusa pomocniczego, są więc pewną specyficzną dodatkową strukturą. W dodatku, niemal nieopisaną w polskich publikacjach. Sądzę więc, że napomknięcie o nich w Pana publikacji, choćby na zasadzie wtrącenia jak o prionach, będzie bardzo użyteczne i zainteresowana osoba, która natrafi na tę kwestię będzie miała szansę poznać te terminy i dalej szukać (ja miałem tak z nanobami :).
> Czy mógłbym więc Pana prosić o zamieszczenie choćby luźnego napomknięcia o tych dwóch strukturach?, które również z organizmami pewien (podobny do wiroidów czy prionów) związek mają
> Pozwolę sobie również przy okazji bardzo podziękować za tę publikację. Jest mi ona niezwykle pomocna (co prawda w zakresie stricte hobbystycznym:), ale no wręcz zbawienna!
> Z poważaniem i ogromnym podziękowaniem,

> AD

> Nie znaleziono wirusów w tej wiadomości.
> Sprawdzone przez AVG – www.avg.com
> Wersja: 2015.0.6081 / Baza danych wirusów: 4392/10323 – Data wydania: 2015–07–28

> Nie znaleziono wirusów w tej wiadomości.
> Sprawdzone przez AVG – www.avg.com
> Wersja: 2015.0.6125 / Baza danych wirusów: 4392/10469 – Data wydania: 2015–08–19

Group I: dsDNA viruses
HHV-6 genome
Genome of human herpesvirus-6, a member of the family Herpesviridae
Genome organization within this group varies considerably. Some have circular genomes (Baculoviridae, Papovaviridae and Polydnaviridae) while others have linear genomes (Adenoviridae, Herpesviridae and some phages). Some families have circularly permuted linear genomes (phage T4 and some Iridoviridae). Others have linear genomes with covalently closed ends (Poxviridae and Phycodnaviridae).

A virus infecting archaea was first described in 1974. Several others have been described since: most have head-tail morphologies and linear double-stranded DNA genomes. Other morphologies have also been described: spindle shaped, rod shaped, filamentous, icosahedral and spherical. Additional morphological types may exist.

Orders within this group are defined on the basis of morphology rather than DNA sequence similarity. It is thought that morphology is more conserved in this group than sequence similarity or gene order which is extremely variable. Three orders and 31 families are currently recognised. A fourth order – Megavirales – for the nucleocytoplasmic large DNA viruses has been proposed.[1][2] This proposal has yet to be ratified by the ICTV. Four genera are recognised that have not yet been assigned a family.

Fifteen families are enveloped. These include all three families in the order Herpesvirales and the following families: Ascoviridae, Ampullaviridae, Asfarviridae, Baculoviridae, Fuselloviridae, Globuloviridae, Guttaviridae, Hytrosaviridae, Iridoviridae, Lipothrixviridae, Nimaviridae and Poxviridae.

Bacteriophages (viruses infecting bacteria) belonging to the families Tectiviridae and Corticoviridae have a lipid bilayer membrane inside the icosahedral protein capsid and the membrane surrounds the genome. The crenarchaeal virus Sulfolobus turreted icosahedral virus has a similar structure.

The genomes in this group vary considerably from ~10 kilobases to over 2.5 megabases in length. The largest bacteriophage known is Klebsiella Phage vB_KleM-RaK2 which has a genome of 346 kilobases.[3]

The virophages are a group of viruses that infect other viruses.

A virus with a novel method of genome packing infecting species of the genus Sulfolobus has been described.[4] As this virus does not resemble any known virus it has been classified into a new family, the Portogloboviridae.

Another Sulfolobus infecting virus—Sulfolobus ellipsoid virus 1—has been described.[5] This enveloped virus has a unique capsid and may be classified into a new taxon.

Host range
Species of the order Caudovirales and of the families Corticoviridae and Tectiviridae infect bacteria.

Species of the order Ligamenvirales and the families Ampullaviridae, Bicaudaviridae, Clavaviridae, Fuselloviridae, Globuloviridae, Guttaviridae , Tristromaviridae and Turriviridae infect hyperthermophilic archaea species of the Crenarchaeota.

Species of the order Herpesvirales and of the families Adenoviridae, Asfarviridae, Iridoviridae, Papillomaviridae, Polyomaviridae and Poxviridae infect vertebrates.

Species of the families Ascovirus, Baculovirus, Hytrosaviridae, Iridoviridae and Polydnaviruses and of the genus Nudivirus infect insects.

Species of the family Mimiviridae and the species Marseillevirus, Megavirus, Mavirus virophage and Sputnik virophage infect Protozoa.

Species of the family Nimaviridae infect crustaceans.

Species of the family Phycodnaviridae and the species Organic Lake virophage infect algae. These are the only known dsDNA viruses that infect plants.

Species of the family Plasmaviridae infect species of the class Mollicutes.

Species of the family Pandoraviridae infect amoebae.

Species of the genus Dinodnavirus infect dinoflagellates. These are the only known viruses that infect dinoflagellates.

Species of the genus Rhizidiovirus infect stramenopiles. These are the only known dsDNA viruses that infect stramenopiles.

Species of the genus Salterprovirus and Sphaerolipoviridae infect species of the Euryarchaeota.

Taxonomy
Order Caudovirales
Family Myoviridae—includes Enterobacteria phage T4
Family Podoviridae—includes Enterobacteria phage T7
Family Siphoviridae—includes Enterobacteria phage λ
Order Herpesvirales
Family Alloherpesviridae
Family Herpesviridae—includes human herpesviruses, Varicella Zoster virus
Family Malacoherpesviridae
Order Ligamenvirales
Family Lipothrixviridae
Family Rudiviridae
Unassigned families
Family Adenoviridae—includes viruses which cause human adenovirus infection
Family Ampullaviridae
Family Ascoviridae
Family Asfarviridae—includes African swine fever virus
Family Baculoviridae
Family Bicaudaviridae
Family Clavaviridae
Family Corticoviridae
Family Fuselloviridae
Family Globuloviridae
Family Guttaviridae
Family Hytrosaviridae
Family Iridoviridae
Family Lavidaviridae
Family Marseilleviridae
Family Mimiviridae
Family Nudiviridae
Family Nimaviridae
Family Pandoraviridae
Family Papillomaviridae
Family Phycodnaviridae
Family Plasmaviridae
Family Polydnaviruses
Family Polyomaviridae—includes Simian virus 40, JC virus, BK virus
Family Poxviridae—includes Cowpox virus, smallpox
Family Sphaerolipoviridae
Family Tectiviridae
Family Tristromaviridae
Family Turriviridae
Unassigned genera
Dinodnavirus
Salterprovirus
Rhizidiovirus
Unassigned species
Abalone shriveling syndrome-associated virus
Bandicoot papillomatosis carcinomatosis virus
Cedratvirus
Kaumoebavirus
KIs-V
Lentille virus
Leptopilina boulardi filamentous virus
Megavirus
Metallosphaera turreted icosahedral virus
MetSV
Methanosarcina spherical virus
Mollivirus sibericum virus
Orpheovirus IHUMI-LCC2
Phaeocystis globosa virus
Pithovirus
Virophages
Family Lavidaviridae
Organic Lake virophage
Ace Lake Mavirus virophage
Dishui Lake virophage 1
Guarani virophage
Phaeocystis globosa virus virophage
Rio Negro virophage
Sputnik virophage 2
Yellowstone Lake virophage 1
Yellowstone Lake virophage 2
Yellowstone Lake virophage 3
Yellowstone Lake virophage 4
Yellowstone Lake virophage 5
Yellowstone Lake virophage 6
Yellowstone Lake virophage 7
Zamilon virophage 2
Unclassified viruses
A group of double stranded DNA viruses have been found in fish that appear to be related to the herpesviruses.[6]

Another group of viruses that infect fish has been described.[7]

Pleolipoviruses
A group known as the pleolipoviruses, although having a similar genome organisation, differ in having either single or double stranded DNA genomes.[8] Within the double stranded forms have runs of single stranded DNA.[9] These viruses have been placed in the family Pleolipoviridae.[10] This family has been divided in three genera: Alphapleolipovirus, Betapleolipovirus and Gammapleolipovirus.

These viruses are nonlytic and form virions characterized by a lipid vesicle enclosing the genome.[8] They do not have nucleoproteins. The lipids in the viral membrane are unselectively acquired from host cell membranes. The virions contain two to three major structural proteins, which either are embedded in the membrane or form spikes distributed randomly on the external membrane surface.

This group includes the following viruses:[11]

Genus: Alphapleolipovirus
Haloarcula hispanica pleomorphic virus 1 (Haloarcula virus HHPV1)
Haloarcula hispanica pleomorphic virus 2 (Haloarcula virus HHPV2)
Halorubrum pleomorphic virus 1
Halorubrum pleomorphic virus 2
Halorubrum pleomorphic virus 6
Genus: Betapleolipovirus
Halogeometricum pleomorphic virus 1 (Halogeometricum virus HGPV1)
Halorubrum pleomorphic virus 3 (Halorubrum virus HRPV3)
SNJ2 [12]
Genus: Gammapleolipovirus
Haloarcula virus His2
Group II: ssDNA viruses

Genome of bacteriophage ΦX174, a single-stranded DNA virus
Although bacteriophages were first described in 1927, it was only in 1959 that Sinshemer working with phage Phi X 174 showed that they could possess single-stranded DNA genomes.[13][14] Despite this discovery, until relatively recently it was believed that most DNA viruses contained double-stranded DNA. Recent work, however, has shown that single-stranded DNA viruses can be highly abundant in seawater, freshwater, sediments, terrestrial and extreme environments, as well as metazoan-associated and marine microbial mats.[15][16][17] Many of these “environmental” viruses belong to the family Microviridae.[18] However, the vast majority has yet to be classified and assigned to genera and higher taxa. Because most of these viruses do not appear to be related, or are only distantly related to known viruses, additional taxa will have to be created to accommodate them.

Archaea
Although ~50 archaeal viruses are known, all but two have double stranded genomes. These two viruses have been placed in the families Pleolipoviridae and Spiraviridae

Taxonomy
Families in this group have been assigned on the basis of the nature of the genome (circular or linear) and the host range. Eleven families are currently recognised.

Family Anelloviridae
Family Bacilladnaviridae
Family Bidnaviridae
Family Circoviridae
Family Geminiviridae
Family Genomoviridae
Family Inoviridae
Family Microviridae
Family Nanoviridae
Family Parvoviridae
Family Smacoviridae
Family Spiraviridae
Classification
A division of the circular single stranded viruses into four types has been proposed.[19] This division seems likely to reflect their phylogenetic relationships.

Type I genomes are characterized by a small circular DNA genome (approximately 2-kb), with the Rep protein and the major open reading frame (ORF) in opposite orientations. This type is characteristic of the circoviruses, geminiviruses and nanoviruses.

Type II genomes have the unique feature of two separate Rep ORFs.

Type III genomes contain two major ORFs in the same orientation. This arrangement is typical of the anelloviruses.

Type IV genomes have the largest genomes of nearly 4-kb, with up to eight ORFs. This type of genome is found in the Inoviridae and the Microviridae.

Given the variety of single stranded viruses that have been described this scheme—if it is accepted by the ICTV—will need to be extended.

CRESS DNA viruses
All known eukaryotic ssDNA viruses also form icosahedral capsids. With the exception of the family Bidnaviridae and Anelloviridae, all eukaryotic ssDNA viruses encode homologous rolling-circle replication initiation proteins with characteristic N-terminal endonuclease domains and C-terminal superfamily three helicase domains.[20] A name for this group of viruses has been proposed—circular Rep-encoding single-strand (CRESS) DNA viruses.[21] It has been proposed that CRESS-DNA viruses have evolved from bacterial plasmids, from which they inherited the Rep genes.[22]

Cruciviridae
A group of ssDNA viruses whose Rep proteins show homology to ssDNA viruses from the families Geminiviridae, Circoviridae, and Nanoviridae, while their coat protein is related to those of ssRNA viruses from the family Tombusviridae and unclassified oomycete-infecting viruses.[23] The name Cruciviridae has been proposed for this group.[24]

Host range
The families Bidnaviridae and Parvoviridae have linear genomes while the other families have circular genomes. The Bidnaviridae have a two part genome and infect invertebrates. The Inoviridae and Microviridae infect bacteria; the Anelloviridae and Circoviridae infect animals (mammals and birds respectively); and the Geminiviridae and Nanoviridae infect plants. In both the Geminiviridae and Nanoviridae the genome is composed of more than a single chromosome. The Bacillariodnaviridae infect diatoms and have a unique genome: the major chromosome is circular (~6 kilobases in length): the minor chromosome is linear (~1 kilobase in length) and complementary to part of the major chromosome. Members of the Spiraviridae infect archaea. Members of the Genomoviridae infect fungi.

Molecular biology
All viruses in this group require formation of a replicative form—a double stranded DNA intermediate—for genome replication. This is normally created from the viral DNA with the assistance of the host's own DNA polymerase.

Recently classified viruses
In the 9th edition of the viral taxonomy of the ICTV (published 2011) the Bombyx mori densovirus type 2 was placed in a new family—the Bidnaviridae on the basis of its genome structure and replication mechanism. This is currently the only member of this family but it seems likely that other species will be allocated to this family in the near future.

A new genus – Bufavirus – was proposed on the basis of the isolation of two new viruses from human stool.[25] Another member of this genus—megabat bufavius 1—has been reported from bats.[26] The human viruses have since been renamed Primate protoparvovirus and been placed in the genus Protoparvovirus.[27][28]

Another proposed genus is Pecovirus. These are similar in organisation to the Smacovirus but share little sequence similarity.

Genomoviridae
The most recently introduced family of ssDNA viruses is the Genomoviridae (the family name is an acronym derived from geminivirus-like, no movement protein).[29]

The family includes 9 genera, namely Gemycircularvirus, Gemyduguivirus, Gemygorvirus, Gemykibivirus, Gemykolovirus, Gemykrogvirus, Gemykroznavirus, Gemytondvirus and Gemyvongvirus.[30]

The genus name Gemycircularvirus stands for Gemini-like myco-infecting circular virus.[31][32] the type species of the genus Gemycircularvirus—Sclerotinia sclerotiorum hypovirulence associated DNA virus 1—is currently the only cultivated member of the family.[29] The rest of genomoviruses are uncultivated and have been discovered using metagenomics techniques.[30]

Another genus has been proposed—Gemybolavirus.[33]

Human isolates
Isolates from this group have also been isolated from the cerebrospinal fluid and brains of patients with multiple sclerosis.[34]

A isolate from this group has also been identified in a child with encephalitis.[35]

Viruses from this group have also been isolated from the blood of HIV+ve patients.[36]

Animal isolates
Ostrich faecal associated ssDNA virus has been placed in the genus Gemytondvirus. Rabbit faecal associated ssDNA virus has been placed in the genus Gemykroznavirus.

Another virus from this group has been isolated from mosquitoes.[37]

Ten new circular viruses have been isolated from dragonfly larvae.[38] The genomes range from 1628 to 2668 nucleotides in length. These dragonfly viruses have since been placed in the Gemycircularviridae.

Additional viruses from this group have been reported from dragonflies and damselflies.[39]

Plants and fungi
Three viruses in this group have been isolated from plants.[40]

A virus – Cassava associated circular DNA virus – that has some similarity to Sclerotinia sclerotiorum hypovirulence associated DNA virus 1 has been isolated.[41] This virus has been placed in the Gemycircularviridae.

Some of this group of viruses may infect fungi.[42]

Smacoviridae
A new family, the Smacoviridae, has been created for a number of single-stranded DNA viruses isolated from the faeces of various mammals.[43] Smacoviruses have circular genomes of ~2.5 kilobases and have a Rep protein and capsid protein encoded in opposite orientations. 43 species have been included in this family which includes six genera – Bovismacovirus, Cosmacovirus, Dragsmacovirus, Drosmacovirus, Huchismacovirus and Porprismacovirus.

Unassigned species
A number of additional single stranded DNA viruses have been described but are as yet unclassified.

Human isolates
Viruses in this group have been isolated from other cases of encephalitis, diarrhoea and sewage.[44]

Two viruses have been isolated from human faeces—circo-like virus Brazil hs1 and hs2—with genome lengths of 2526 and 2533 nucleotides respectively.[45] These viruses have four open reading frames. These viruses appear to be related to three viruses previously isolated from waste water, a bat and from a rodent.[46] This appears to belong to a novel group.

A novel species of virus – human respiratory-associated PSCV-5-like virus—has been isolated from the respiratory tract.[47] The virus is approximately 3 kilobases in length and has two open reading frames—one encoding the coat protein and the other the DNA replicase. The significance—if any—of this virus for human disease is unknown presently.

Animal viruses – vertebrates
An unrelated group of ssDNA viruses, also discovered using viral metagenomics, includes the species bovine stool associated circular virus and chimpanzee stool associated circular virus.[48] The closest relations to this genus appear to be the Nanoviridae but further work will be needed to confirm this. Another isolate that appears to be related to these viruses has been isolated from pig faeces in New Zealand.[49] This isolate also appears to be related to the pig stool-associated single-stranded DNA virus. This virus has two large open reading frames one encoding the capsid gene and the other the Rep gene. These are bidirectionally transcribed and separated by intergenic regions. Another virus of this group has been reported again from pigs.[50] A virus from this group has been isolated from turkey faeces.[51] Another ten viruses from this group have been isolated from pig faeces.[52] Viruses that appear to belong to this group have been isolated from other mammals including cows, rodents, bats, badgers and foxes.[42]

Another virus in this group has been isolated from birds.[53]

Fur seal feces-associated circular DNA virus was isolated from the faeces of a fur seal (Arctocephalus forsteri) in New Zealand.[54] The genome has 2 main open reading frames and is 2925 nucleotides in length. Another virus—porcine stool associated virus 4[55]—has been isolated. It appears to be related to the fur seal virus.

Two viruses have been described from the nesting material yellow crowned parakeet (Cyanoramphus auriceps) – Cyanoramphus nest-associated circular X virus (2308 nt) and Cyanoramphus nest-associated circular K virus (2087 nt)[56] Both viruses have two bidirectional open reading frames. Within these are the rolling-circle replication motifs I, II, III and the helicase motifs Walker A and Walker B. There is also a conserved nonanucleotide motif required for rolling-circle replication. CynNCKV has some similarity to the picobiliphyte nano-like virus (Picobiliphyte M5584–5)[57] and CynNCXV has some similarity to the rodent stool associated virus (RodSCV M-45).[58]

A virus with a circular genome – sea turtle tornovirus 1 – has been isolated from a sea turtle with fibropapillomatosis.[59] It is sufficiently unrelated to any other known virus that it may belong to a new family. The closest relations seem to be the Gyrovirinae. The proposed genus name for this virus is Tornovirus.

Another faecal virus—feline stool-associated circular DNA virus—has been described.[60]

Animal viruses – invertebrates
Among these are the parvovirus-like viruses. These have linear single-stranded DNA genomes but unlike the parvoviruses the genome is bipartate. This group includes Hepatopancreatic parvo-like virus and Lymphoidal parvo-like virus. A new family Bidensoviridae has been proposed for this group but this proposal has not been ratified by the ICTV to date.[61] Their closest relations appear to be the Brevidensoviruses (family Parvoviridae).[62]

A virus – Acheta domesticus volvovirus—has been isolated from the house cricket (Acheta domesticus).[63] The genome is circular, has four open reading frames and is 2,517 nucleotides in length. It appears to be unrelated to previously described species. The genus name Volvovirus has been proposed for these species.[64] The genomes in this genus are ~2.5 nucleotides in length and encode 4 open reading frames.

Two new viruses have been isolated from the copepods Acartia tonsa and Labidocera aestiva— Acartia tonsa copepod circo-like virus and Labidocera aestiva copepod circo-like virus respectively.

A virus has been isolated from the mud flat snail (Amphibola crenata).[65] This virus has a single stranded circular genome of 2351 nucleotides that encoded 2 open reading frames that are oriented in opposite directions. The smaller open reading frame (874 nucleotides) encodes a protein with similarities to the Rep (replication) proteins of circoviruses and plasmids. The larger open reading frame (955 nucleotides) has no homology to any currently known protein.[citation needed]

An unusual – and as yet unnamed – virus has been isolated from the flatworm Girardia tigrina.[66] Because of its genome organisation, this virus appears to belong to an entirely new family. It is the first virus to be isolated from a flatworm.

From the hepatopancreas of the shrimp (Farfantepenaeus duorarum) a circular single stranded DNA virus has been isolated.[67] This virus does not appear to cause disease in the shrimp.

A circo-like virus has been isolated from the shrimp (Penaeus monodon).[68] The 1,777-nucleotide genome is circular and single stranded. It has some similarity to the circoviruses and cycloviruses.

Ten viruses have been isolated from echinoderms.[69] All appear to belong to as yet undescribed genera.

A filamentous virus—Apis mellifera filamentous virus—has been described.[70] It appears to be unrelated to other DNA viruses.

Plants
A circular single stranded DNA virus has been isolated from a grapevine.[71] This species may be related to the family Geminiviridae but differs from this family in a number of important respects including genome size.

Several viruses – baminivirus, nepavirus and niminivirus – related to geminvirus have also been reported.[42]

A virus—Ancient caribou feces associated virus—has been cloned from 700-y-old caribou faeces.[72]

A new virus with a three part single stranded genome has been reported.[73] This seems likely to be a member of a new family of viruses.

Marine and other
More than 600 single-stranded DNA viral genomes were identified in ssDNA purified from seawater .[15] These fell into 129 genetically distinct groups that had no recognizable similarity to each other or to other virus sequences, and thus many likely represent new families of viruses. Of the 129 groups, eleven were much more abundant than the others, and although their hosts have yet to be identified, they are likely to be eukaryotic phytoplankton, zooplankton and bacteria.[citation needed]

A virus – Boiling Springs Lake virus – appears to have evolved by a recombination event between a DNA virus (circovirus) and an RNA virus (tombusvirus).[23] The genome is circular and encodes two proteins—a Rep protein and a capsid protein.

Further reports of viruses that appear to have evolved from recombination events between ssRNA and ssDNA viruses have been made.[74]

A new virus has been isolated from the diatom Chaetoceros setoensis.[75] It has a single stranded DNA genome and does not appear to be a member of any previously described group.

A virus—FLIP (Flavobacterium-infecting, lipid-containing phage)—has been isolated from a lake.[76] This virus has a circular ssDNA genome (9,174 nucleotides) and an internal lipid membrane enclosed in an icosahedral capsid. The capsid organisation is he capsid organization pseudo T = 21 dextro. The major capsid protein has two β-barrels. The capsid organisation is similar to bacteriophage PM2—a double stranded bacterial virus.[citation needed]

Satellite viruses
Satellite viruses are small viruses with either RNA or DNA as their genomic material that require another virus to replicate. There are two types of DNA satellite viruses—the alphasatellites and the betasatellites—both of which are dependent on begomoviruses. At present satellite viruses are not classified into genera or higher taxa.

Alphasatellites are small circular single strand DNA viruses that require a begomovirus for transmission. Betasatellites are small linear single stranded DNA viruses that require a begomovirus to replicate.

Phylogenetic relationships
Introduction
Phylogenetic relationships between these families are difficult to determine. The genomes differ significantly in size and organisation. Most studies that have attempted to determine these relationships are based either on some of the more conserved proteins—DNA polymerase and others—or on common structural features. In general most of the proposed relationships are tentative and have not yet been used by the ICTV in their classification.

ds DNA viruses
Herpesviruses and caudoviruses
While determining the phylogenetic relations between the various known clades of viruses is difficult, on a number of grounds the herpesviruses and caudoviruses appear to be related.

While the three families in the order Herpesvirales are clearly related on morphological grounds, it has proven difficult to determine the dates of divergence between them because of the lack of gene conservation.[77] On morphological grounds they appear to be related to the bacteriophages—specifically the Caudoviruses.

The branching order among the herpesviruses suggests that Alloherpesviridae is the basal clade and that Herpesviridae and Malacoherpesviridae are sister clades.[78] Given the phylogenetic distances between vertebrates and molluscs this suggests that herpesviruses were initially fish viruses and that they have evolved with their hosts to infect other vertebrates.

The vertebrate herpesviruses initially evolved ~400 million years ago and underwent subsequent evolution on the supercontinent Pangaea.[79] The alphaherpesvirinae separated from the branch leading to the betaherpesvirinae and gammaherpesvirinae about 180 million years ago to 220 million years ago.[80] The avian herpes viruses diverged from the branch leading to the mammalian species.[81] The mammalian species divided into two branches—the Simplexvirus and Varicellovirus genera. This latter divergence appears to have occurred around the time of the mammalian radiation.

Several dsDNA bacteriophages and the herpesviruses encode a powerful ATP driven DNA translocating machine that encapsidates a viral genome into a preformed capsid shell or prohead. The critical components of the packaging machine are the packaging enzyme (terminase) which acts as the motor and the portal protein that forms the unique DNA entrance vertex of prohead. The terminase complex consists of a recognition subunit (small terminase) and an endonuclease/translocase subunit (large terminase) and cuts viral genome concatemers. It forms a motor complex containing five large terminase subunits. The terminase-viral DNA complex docks on the portal vertex. The pentameric motor processively translocates DNA until the head shell is full with one viral genome. The motor cuts the DNA again and dissociates from the full head, allowing head-finishing proteins to assemble on the portal, sealing the portal, and constructing a platform for tail attachment. Only a single gene encoding the putative ATPase subunit of the terminase (UL15) is conserved among all herpesviruses. To a lesser extent this gene is also found in T4-like bacteriophages suggesting a common ancestor for these two groups of viruses.[82] Another paper has also suggested that herpesviruses originated among the bacteriophages.[83]

A common origin for the herpesviruses and the caudoviruses has been suggested on the basis of parallels in their capsid assembly pathways and similarities between their portal complexes, through which DNA enters the capsid.[84] These two groups of viruses share a distinctive 12-fold arrangement of subunits in the portal complex. A second paper has suggested an evolutionary relationship between these two groups of viruses.[83]

It seems likely that the tailed viruses infecting the archaea are also related to the tailed viruses infecting bacteria.[85][86]

A study involving 600 herpes genomes and 2000 caudoviral genomes suggested that an evolutionary relationship exists between these order.[87]

Large DNA viruses
The nucleocytoplasmic large DNA virus group (Asfarviridae, Iridoviridae, Marseilleviridae, Mimiviridae, Phycodnaviridae and Poxviridae) along with three other families—Adenoviridae, Cortiviridae and Tectiviridae— and the phage Sulfolobus turreted icosahedral virus and the satellite virus Sputnik all possess double β-barrel major capsid proteins suggesting a common origin.[88]

Several studies have suggested that the family Ascoviridae evolved from the Iridoviridae.[89][90][91][92] A study of the Iridoviruses suggests that the Iridoviridae, Ascoviridae and Marseilleviridae are related with Ascoviruses most closely related to Iridoviruses.[93]

The family Polydnaviridae may have evolved from the Ascoviridae.[94] Molecular evidence suggests that the Phycodnaviridae may have evolved from the family Iridoviridae.[95] These four families (Ascoviridae, Iridoviridae, Phycodnaviridae and Polydnaviridae) may form a clade but more work is needed to confirm this.

Some of the relations among the large viruses have been established.[96] Mimiviruses are distantly related to Phycodnaviridae. Pandoraviruses share a common ancestor with Coccolithoviruses within the family Phycodnaviridae.[97] Pithoviruses are related to Iridoviridae and Marseilleviridae.

Based on the genome organisation and DNA replication mechanism it seems that phylogenetic relationships may exist between the rudiviruses (Rudiviridae) and the large eukaryal DNA viruses: the African swine fever virus (Asfarviridae), Chlorella viruses (Phycodnaviridae) and poxviruses (Poxviridae).[98]

Based on the analysis of the DNA polymerase the genus Dinodnavirus may be a member of the family Asfarviridae.[99] Further work on this virus will required before a final assignment can be made.

It has been suggested that at least some of the giant viruses may originate from mitochondria.[100]

Other viruses
Based on the analysis of the coat protein, Sulfolobus turreted icosahedral virus may share a common ancestry with the Tectiviridae.

The families Adenoviridae and Tectiviridae appear to be related structurally.[101]

Baculoviruses evolved from the nudiviruses 310 million years ago.[102][103]

The Hytrosaviridae are related to the baculoviruses and to a lesser extent the nudiviruses suggesting they may have evolved from the baculoviruses.[104]

The Nimaviridae may be related to nudiviruses and baculoviruses.[105]

The Nudiviruses seem to be related to the polydnaviruses.[106]

A protein common to the families Bicaudaviridae, Lipotrixviridae and Rudiviridae and the unclassified virus Sulfolobus turreted icosahedral virus is known suggesting a common origin.[107]

Examination of the pol genes that encode the DNA dependent DNA polymerase in various groups of viruses suggests a number of possible evolutionary relationships.[108] All know viral DNA polymerases belong to the DNA pol families A and B. All possess a 3'-5'-exonuclease domain with three sequence motifs Exo I, Exo II and Exo III. The families A and B are distinguishable with family A Pol sharing 9 distinct consensus sequences and only two of them are convincingly homologous to sequence motif B of family B. The putative sequence motifs A, B, and C of the polymerase domain are located near the C-terminus in family A Pol and more central in family B Pol.[citation needed]

Phylogenetic analysis of these genes places the adenoviruses (Adenoviridae), bacteriophages (Caudovirales) and the plant and fungal linear plasmids into a single clade. A second clade includes the alpha- and delta-like viral Pol from insect ascovirus (Ascoviridae), mammalian herpesviruses (Herpesviridae), fish lymphocystis disease virus (Iridoviridae) and chlorella virus (Phycoviridae). The pol genes of the African swine fever virus (Asfarviridae), baculoviruses (Baculoviridae), fish herpesvirus (Herpesviridae), T-even bacteriophages (Myoviridae) and poxviruses (Poxviridae) were not clearly resolved. A second study showed that poxvirus, baculovirus and the animal herpesviruses form separate and distinct clades.[109] Their relationship to the Asfarviridae and the Myoviridae was not examined and remains unclear.

The polymerases from the archaea are similar to family B DNA Pols. The T4-like viruses infect both bacteria and archaea[110] and their pol gene resembles that of eukaryotes. The DNA polymerase of mitochondria resembles that of the T odd phages (Myoviridae).[111]

The virophage—Mavirus—may have evolved from a recombination between a transposon of the Polinton (Maverick) family and an unknown virus.[112]

The polyoma and papillomaviruses appear to have evolved from single-stranded DNA viruses and ultimately from plasmids.[83]

ss DNA viruses
The evolutionary history of this group is currently poorly understood. An ancient origin for the single stranded circular DNA viruses has been proposed.[113]

Capsid proteins of most icosahedral ssRNA and ssDNA viruses display the same structural fold, the eight-stranded beta-barrel, also known as the jelly-roll fold. On the other hand, the replication proteins of icosahedral ssDNA viruses belong to the superfamily of rolling-circle replication initiation proteins that are commonly found in prokaryotic plasmids.[114] Based on these observations, it has been proposed that small DNA viruses have originated via recombination between RNA viruses and plasmids.[115][116]

Circoviruses may have evolved from a nanovirus.[117][118][119]

Given the similarities between the rep proteins of the alphasatellites and the nanoviruses, it is likely that the alphasatellites evolved from the nanoviruses.[120] Further work in this area is needed to clarify this.

The geminiviruses may have evolved from phytoplasmal plasmids.[121] The Genomoviridae and the Geminividiae appear to be related.

Based on the three-dimensional structure of the Rep proteins the geminiviruses and parvoviruses may be related.[122]

The ancestor of the geminiviruses probably infected dicots.[123]

The parvoviruses have frequently invaded the germ lines of diverse animal species including mammals, fishes, birds, tunicates, arthropods and flatworms.[124][125] In particular they have been associated with the human genome for ~98 million years.

Members of the family Bidnaviridae have evolved from insect parvoviruses by replacing the typical replication-initiation endonuclease with a protein-primed family B DNA polymerase acquired from large DNA transposons of the Polinton/Maverick family. Some bidnavirus genes were also horizontally acquired from reoviruses (dsRNA genomes) and baculoviruses (dsDNA genomes).[126]

Bacteriophage evolution
Since 1959 ~6300 prokaryote viruses have been described morphologically, including ~6200 bacterial and ~100 archaeal viruses.[127] Archaeal viruses belong to 15 families and infect members of 16 archaeal genera. These are nearly exclusively hyperthermophiles or extreme halophiles. Tailed archaeal viruses are found only in the Euryarchaeota, whereas most filamentous and pleomorphic archaeal viruses occur in the Crenarchaeota. Bacterial viruses belong to 10 families and infect members of 179 bacterial genera: most these are members of the Firmicutes and γ-proteobacteria.

The vast majority (96.3%) are tailed with and only 230 (3.7%) are polyhedral, filamentous or pleomorphic. The family Siphoviridae is the largest family (>3600 descriptions: 57.3%). The tailed phages appear to be monophyletic and are the oldest known virus group.[128] They arose repeatedly in different hosts and there are at least 11 separate lines of descent.

All of the known temperate phages employ one of only three different systems for their lysogenic cycle: lambda-like integration/excision, Mu-like transposition or the plasmid-like partitioning of phage N15.

A putative course of evolution of these phages has been proposed by Ackermann.[129]

Tailed phages originated in the early Precambrian, long before eukaryotes and their viruses. The ancestral tailed phage had an icosahedral head of about 60 nanometers in diameter and a long non contractile tail with sixfold symmetry. The capsid contained a single molecule of double stranded DNA of about 50 kilobases. The tail was probably provided with a fixation apparatus. The head and tail were held together by a connector. The viral particle contained no lipids, was heavier than its descendant viruses and had a high DNA content proportional to its capsid size (~50%). Most of the genome coded for structural proteins. Morphopoietic genes clustered at one end of the genome, with head genes preceding tail genes. Lytic enzymes were probably coded for. Part of the phage genome was nonessential and possibly bacterial.

The virus infected its host from the outside and injected its DNA. Replication involved transcription in several waves and formation of DNA concatemers.

New phages were released by burst of the infected cell after lysis of host membranes by a peptidoglycan hydrolase. Capsids were assembled from a starting point, the connector and around a scaffold. They underwent an elaborate maturation process involving protein cleavage and capsid expansion. Heads and tails were assembled separately and joined later. The DNA was cut to size and entered preformed capsids by a headful mechanism.

Subsequently, the phages evolved contractile or short tails and elongated heads. Some viruses become temperate by acquiring an integrase-excisionase complex, plasmid parts or transposons.

A possible evolutionary pathway using vesicles rather than a protein coat has been described in the archaeal plasmid pR1SE.[130]

NCLDVs
Main article: Nucleocytoplasmic large DNA viruses
The asfarviruses, iridoviruses, mimiviruses, phycodnaviruses and poxviruses have been shown to belong to a single group,[131]—the large nuclear and cytoplasmic DNA viruses. These are also abbreviated “NCLDV”.[132] This clade can be divided into two groups:

the iridoviruses-phycodnaviruses-mimiviruses group. The phycodnaviruses and mimiviruses are sister clades.
the poxvirus-asfarviruses group.
It is probable that these viruses evolved before the separation of eukaryoyes into the extant crown groups. The ancestral genome was complex with at least 41 genes including (1) the replication machinery (2) up to four RNA polymerase subunits (3) at least three transcription factors (4) capping and polyadenylation enzymes (5) the DNA packaging apparatus (6) and structural components of an icosahedral capsid and the viral membrane.

The evolution of this group of viruses appears to be complex with genes having been gained from multiple sources.[133] It has been proposed that the ancestor of NCLDVs has evolved from large, virus-like DNA transposons of the Polinton/Maverick family.[134] From Polinton/Maverick transposons NCLDVs might have inherited the key components required for virion morphogenesis, including the major and minor capsid proteins, maturation protease and genome packaging ATPase.[135]

Another group of large viruses—the Pandoraviridae—has been described. Two species—Pandoravirus salinus and Pandoravirus dulcis—have been recognized. These were isolated from Chile and Australia respectively. These viruses are about one micrometer in diameter making them one of the largest viruses discovered so far. Their gene complement is larger than any other known virus to date. At present they appear to be unrelated to any other species of virus.[136]

An even larger genus, Pithovirus, has since been discovered, measuring about 1.5 µm in length.[137] Another virus – Cedratvirus – may be related this group.[138]

Double-stranded (ds) RNA viruses are a diverse group of viruses that vary widely in host range (animals, plants, fungi, and bacteria), genome segment number (one to twelve) and virion organization (T-number, capsid layers or turrets). Members of this group include the rotaviruses, known globally as a common cause of gastroenteritis in young children, and bluetongue virus, an economically important pathogen of cattle and sheep.

Of these families, the Reoviridae is the largest and most diverse in terms of host range.

In recent years the increasing knowledge of virus particle assembly, virus-cell interactions, and viral pathogenesis allow approaches for the development of novel antiviral strategies or agents.[1]

Contents
1 Taxonomy
1.1 Taxa
2 Notes on selected species
2.1 Reoviridae
2.1.1 Orthoreoviruses
2.1.2 Cypovirus
2.1.3 Rotavirus
2.1.4 Bluetongue virus
2.1.5 Phytoreoviruses
2.2 The yeast dsRNA virus L-A
2.3 Infectious bursal disease virus
2.4 dsRNA bacteriophage Φ6
3 Anti-virals
4 See also
5 References
6 Bibliography
Taxonomy
Viruses with dsRNA genomes are currently grouped into a number of families, unassigned genera and species.

Three families infect fungi: Totiviridae, Partitiviridae and Chrysoviridae. These families have monopartite, bipartite and quadripartite genomes respectively. They are typically isometric particles 25–50 nanometers in diameter. Based on sequence similarity of the RNA dependent RNA polymerase, the partitiviruses are probably derived from a totivirus ancestor.[2] A fourth family – Alternaviridae – has recently been described also with quadripartite genome.

Hypoviruses are mycoviruses (fungal viruses) with unencapsidated dsRNA genomes. They may have common ancestry with plant positive strand RNA viruses in supergroup 1 with potyvirus lineages, respectively[2]

A new clade (as yet unnamed) of six viruses infecting filamentous fungi has been reported.[3]

Taxa
Families

Amalgaviridae
Birnaviridae
Chrysoviridae
Cystoviridae
Endornaviridae
Hypoviridae
Megabirnaviridae
Partitiviridae
Picobirnaviridae
Quadriviridae
Reoviridae
Totiviridae
Unassigned species

La France isometric virus
Notes on selected species
Reoviridae
Reoviridae are currently classified into nine genera. The genomes of these viruses consist of 10 to 12 segments of dsRNA, each generally encoding one protein. The mature virions are non-enveloped. Their capsids, formed by multiple proteins, have icosahedral symmetry and are arranged generally in concentric layers. A distinguishing feature of the dsRNA viruses, irrespective of their family association, is their ability to carry out transcription of the dsRNA segments, under appropriate conditions, within the capsid. In all these viruses, the enzymes required for endogenous transcription are thus part of the virion structure.[1]

Orthoreoviruses
The orthoreoviruses (reoviruses) are the prototypic members of the virus Reoviridae family and representative of the turreted members, which comprise about half the genera. Like other members of the family, the reoviruses are non-enveloped and characterized by concentric capsid shells that encapsidate a segmented dsRNA genome. In particular, reovirus has eight structural proteins and ten segments of dsRNA. A series of uncoating steps and conformational changes accompany cell entry and replication. High-resolution structures are known for almost all of the proteins of mammalian reovirus (MRV), which is the best-studied genotype. Electron cryo-microscopy (cryoEM) and X-ray crystallography have provided a wealth of structural information about two specific MRV strains, type 1 Lang (T1L) and type 3 Dearing (T3D).[4]

Cypovirus
The cytoplasmic polyhedrosis viruses (CPVs) form the genus Cypovirus of the family Reoviridae. CPVs are classified into 14 species based on the electrophoretic migration profiles of their genome segments. Cypovirus has only a single capsid shell, which is similar to the orthoreovirus inner core. CPV exhibits striking capsid stability and is fully capable of endogenous RNA transcription and processing. The overall folds of CPV proteins are similar to those of other reoviruses. However, CPV proteins have insertional domains and unique structures that contribute to their extensive intermolecular interactions. The CPV turret protein contains two methylase domains with a highly conserved helix-pair/β-sheet/helix-pair sandwich fold but lacks the β-barrel flap present in orthoreovirus λ2. The stacking of turret protein functional domains and the presence of constrictions and A spikes along the mRNA release pathway indicate a mechanism that uses pores and channels to regulate the highly coordinated steps of RNA transcription, processing, and release.[5]

Rotavirus
Rotavirus is the most common cause of acute gastroenteritis in infants and young children worldwide. This virus contains a dsRNA genome and is a member of the Reoviridae family. The genome of rotavirus consists of eleven segments of dsRNA. Each genome segment codes for one protein with the exception of segment 11, which codes for two proteins. Among the twelve proteins, six are structural and six are non-structural proteins.[6] It is a double-stranded RNA non-enveloped virus

Bluetongue virus
The members of genus Orbivirus within the Reoviridae family are arthropod borne viruses and are responsible for high morbidity and mortality in ruminants. Bluetongue virus (BTV) which causes disease in livestock (sheep, goat, cattle) has been in the forefront of molecular studies for the last three decades and now represents the best understood orbivirus at the molecular and structural levels. BTV, like other members of the family, is a complex non-enveloped virus with seven structural proteins and a RNA genome consisting of 10 variously sized dsRNA segments.[7][8]

Phytoreoviruses
Phytoreoviruses are non-turreted reoviruses that are major agricultural pathogens, particularly in Asia. One member of this family, Rice Dwarf Virus (RDV), has been extensively studied by electron cryomicroscopy and x-ray crystallography. From these analyses, atomic models of the capsid proteins and a plausible model for capsid assembly have been derived. While the structural proteins of RDV share no sequence similarity to other proteins, their folds and the overall capsid structure are similar to those of other Reoviridae.[9]

The yeast dsRNA virus L-A
The L-A dsRNA virus of the yeast Saccharomyces cerevisiae has a single 4.6 kb genomic segment that encodes its major coat protein, Gag (76 kDa) and a Gag-Pol fusion protein (180 kDa) formed by a -1 ribosomal frameshift. L-A can support the replication and encapsidation in separate viral particles of any of several satellite dsRNAs, called M dsRNAs, each of which encodes a secreted protein toxin (the killer toxin) and immunity to that toxin. L-A and M are transmitted from cell to cell by the cytoplasmic mixing that occurs in the process of mating. Neither is naturally released from the cell or enters cells by other mechanisms, but the high frequency of yeast mating in nature results in the wide distribution of these viruses in natural isolates. Moreover, the structural and functional similarities with dsRNA viruses of mammals has made it useful to consider these entities as viruses.[10]

Infectious bursal disease virus
Infectious bursal disease virus (IBDV) is the best-characterized member of the family Birnaviridae. These viruses have bipartite dsRNA genomes enclosed in single layered icosahedral capsids with T = 13l geometry. IBDV shares functional strategies and structural features with many other icosahedral dsRNA viruses, except that it lacks the T = 1 (or pseudo T = 2) core common to the Reoviridae, Cystoviridae, and Totiviridae. The IBDV capsid protein exhibits structural domains that show homology to those of the capsid proteins of some positive-sense single-stranded RNA viruses, such as the nodaviruses and tetraviruses, as well as the T = 13 capsid shell protein of the Reoviridae. The T = 13 shell of the IBDV capsid is formed by trimers of VP2, a protein generated by removal of the C-terminal domain from its precursor, pVP2. The trimming of pVP2 is performed on immature particles as part of the maturation process. The other major structural protein, VP3, is a multifunctional component lying under the T = 13 shell that influences the inherent structural polymorphism of pVP2. The virus-encoded RNA-dependent RNA polymerase, VP1, is incorporated into the capsid through its association with VP3. VP3 also interacts extensively with the viral dsRNA genome.[11]

dsRNA bacteriophage Φ6
Bacteriophage Φ6, is a member of the Cystoviridae family. It infects Pseudomonas bacteria (typically plant-pathogenic P. syringae). It has a three-part, segmented, double-stranded RNA genome, totalling ~13.5 kb in length. Φ6 and its relatives have a lipid membrane around their nucleocapsid, a rare trait among bacteriophages. It is a lytic phage, though under certain circumstances has been observed to display a delay in lysis which may be described as a “carrier state”.[12]

Anti-virals
Since cells do not produce double-stranded RNA during normal nucleic acid metabolism, natural selection has favored the evolution of enzymes that destroy dsRNA on contact. The best known class of this type of enzymes is Dicer. It is hoped that broad-spectrum anti-virals could be synthesized that take advantage of this vulnerability of double-stranded RNA viruses.[13]

A positive-sense single-stranded RNA virus (or (+)ssRNA virus) is a virus that uses positive sense, single-stranded RNA as its genetic material. Single stranded RNA viruses are classified as positive or negative depending on the sense or polarity of the RNA. The positive-sense viral RNA genome can also serve as messenger RNA and can be translated into protein in the host cell. Positive-sense ssRNA viruses belong to Group IV in the Baltimore classification.[1] Positive-sense RNA viruses account for a large fraction of known viruses, including many pathogens such as the hepatitis C virus, West Nile virus, dengue virus, and SARS and MERS coronaviruses, as well as less clinically serious pathogens such as the rhinoviruses that cause the common cold.[2][3][4]

Contents
1 Replication
2 Genome
3 Taxonomic distribution
3.1 Bacteria
3.2 Eukaryotes
4 See also
5 References
Replication
Positive-sense ssRNA viruses have genetic material that can function both as a genome and as messenger RNA; it can be directly translated into protein in the host cell by host ribosomes.[5] The first proteins to be expressed after infection serve genome replication functions; they recruit the positive-strand viral genome to viral replication complexes (VRCs) formed in association with intracellular membranes. VRCs contain proteins of both viral and host cell origin, and may be associated with the membranes of a variety of organelles, often the rough endoplasmic reticulum, but also including membranes derived from mitochondria, vacuoles, the Golgi apparatus, chloroplasts, peroxisomes, plasma membranes, autophagosomal membranes, and novel cytoplasmic compartments.[2] The replication of the positive-sense ssRNA genome proceeds through double-stranded RNA intermediates, and the purpose of replication in these membranous invaginations may be the avoidance of cellular response to the presence of dsRNA. In many cases subgenomic RNAs are also created during replication.[5] After infection, the entirety of the host cell's translation machinery may be diverted to the production of viral proteins as a result of the very high affinity for ribosomes of the viral genome's internal ribosome entry site (IRES) elements; in some viruses, such as poliovirus and rhinoviruses, normal protein synthesis is further disrupted by viral proteases degrading components required to initiate translation of cellular mRNA.[4]

All positive-sense ssRNA virus genomes encode RNA-dependent RNA polymerase (RdRP), a viral protein that synthesizes RNA from an RNA template. Host cell proteins recruited by positive-sense ssRNA viruses during replication include RNA-binding proteins, chaperone proteins, and membrane remodeling and lipid synthesis proteins, which collectively participate in exploiting the cell's secretory pathway for viral replication.[2]

Genome
The genome of a positive-sense ssRNA virus usually contains relatively few genes, usually between three and ten, including an RdRP.[2] Coronaviruses have the largest known RNA genomes, up to 32 kilobases in length, and likely possess replication proofreading mechanisms in the form of a proofreading exoribonuclease, non-structural protein 14, that is otherwise not found in RNA viruses.[6]

Taxonomic distribution
The (+)ssRNA viruses are classified into 3 orders – the Nidovirales, Picornavirales, and Tymovirales – and 33 families, of which 20 are not assigned to an order. A broad range of hosts can be infected by (+)ssRNA viruses, including bacteria (the Leviviridae), eukaryotic microorganisms, plants, invertebrates, and vertebrates.[7] No examples have been described that infect archaea, whose virome is generally much less well-characterized.[7][8]

Bacteria
Among known (+)ssRNA viruses, only the Leviviridae are bacteriophages (that is, viruses that infect bacteria). Known leviviruses infect enterobacteria. Phage with RNA genomes are relatively rare and poorly understood, with only one other recognized group – a family of double-stranded RNA viruses called the Cystoviridae. However, metagenomics has led to the identification of numerous additional novel examples.[9]

Eukaryotes
Positive-sense ssRNA viruses are the most common type of plant virus.[10] Members of the (+)ssRNA picornavirus group are also extremely abundant – to the point of “unexpected dominance” – in marine viruses characterized by metagenomics. These viruses likely infect single-celled eukaryotes.[11]

There are eight families of (+)ssRNA viruses that infect vertebrates, of which four are unenveloped (Picornaviridae, Astroviridae, Caliciviridae, and Hepeviridae) and four are enveloped (Flaviviridae, Togaviridae, Arteriviridae, and Coronaviridae). All but the arterivirus family contain at least one human pathogen; arteriviruses are known only as animal pathogens.[4] Many pathogenic (+)ssRNA viruses are arthropod-borne viruses (also called arboviruses) – that is, transmitted by and capable of replicating in biting insects which then transfer the pathogen to animal hosts. Recent metagenomics studies have also identified large numbers of RNA viruses whose host range is specific to insects.[12]

A negative-sense single-stranded RNA virus (or (−)ssRNA virus) is a virus that uses negative sense, single-stranded RNA as its genetic material. Single stranded RNA viruses are classified as positive or negative depending on the sense or polarity of the RNA. The negative viral RNA is complementary to the mRNA and must be converted to a positive RNA by RNA polymerase before translation. Therefore, the purified RNA of a negative sense virus is not infectious by itself, as it needs to be converted to a positive sense RNA for replication. These viruses belong to Group V on the Baltimore classification.[1]

In addition, negative-sense single-stranded RNA viruses have complex genomic sequences, cell cycles, and replication habits that use various protein complexes to arrange in specific conformations and carry out necessary processes for survival and reproduction of their genomic sequences. The complexity of negative-sense single-stranded RNA viruses carries into its ability to suppress the innate immune response of the cells it infects and the construction of a capsid, which is unique to the varying classifications of negative-sense single-stranded RNA viruses.

Contents
1 Replication
2 Taxonomy
3 Host range
4 Genome
5 NSV Life Cycle and Replication
6 Molecular Mechanisms of Innate Antiviral Immune Inhibition
7 NNSV-Mediated Inhibition of IFN Induction
8 NNSV-Mediated Inhibition of IFN Response
9 Ubiquitination
10 Common Mechanism for RNA Encapsidation by NSVs
11 See also
12 References
13 External links
Replication
Negative sense ssRNA viruses need RNA polymerase to form a positive sense RNA. The positive-sense RNA acts as a viral mRNA, which is translated into proteins for the production of new virion materials. With the newly formed virions, more negative sense RNA molecules are produced.

In more details, replication of the virion consists of the following steps:[2][3][4]

A virion enters the host cell and releases its negative RNA into the cytoplasm.
The virus uses its own RNA replicase, also known as RNA-dependent RNA polymerase (RdRp), to form positive RNA template strands through complementary base pairing.
The positive RNA acts as mRNA, which is translated into structural capsomere proteins and viral RdRp by the host's ribosomes.
A replicative complex is formed with RdRp: The positive strands can either function as mRNA to produce more proteins or as template to make more negative RNA strands.
New viral capsids are assembled with the capsomere proteins. The negative RNA strands combine with capsids and viral RdRp to form new negative RNA virions.
After assembly and maturation of nucleocapsid, the new virions exit the cell by budding or lysing through cell membrane to further infect other cells.
The genome size of a negative RNA virus is between 10kb to 30kb. Two genome subgroups can be distinguished, nonsegmented and segmented, and are described as such:

In viruses with nonsegmented genomes, the first step of replication is transcription of the negative strand by RdRp to form various monocistronic mRNA that code for individual viral proteins. A positive strand copy is formed to serve as template for the production of the negative genome. This replication takes place in the cytoplasm.
In viruses with segmented genomes, replication occurs in the nucleus and the RdRp produces one monocistronic mRNA strand from each genome segment. The principal difference between the two types is the location of replication.
Taxonomy
One phylum, two subphyla, six classes, eight orders and twenty one families are currently recognised in this group.[5] A number of unassigned species and genera are yet to be classified.[6] Outside the all encompassing Negarnaviricota phylum there is only Deltavirus genus.

Phylum Negarnaviricota[7]
Subphylum Haploviricotina
Class Chunqiuviricetes
Order Muvirales
Family Qinviridae
Class Milneviricetes
Order Serpentovirales
Family Aspiviridae
Class Monjiviricetes
Order Jingchuvirales
Order Mononegavirales
Family Bornaviridae – Borna disease virus
Family Filoviridae – includes Ebola virus, Marburg virus
Family Mymonaviridae
Family Nyamiviridae[8]
Family Paramyxoviridae – includes Measles virus, Mumps virus, Nipah virus, Hendra virus, and NDV
Family Pneumoviridae – includes RSV and Metapneumovirus
Family Rhabdoviridae – includes Rabies virus
Family Sunviridae
Genus Anphevirus
Genus Arlivirus
Genus Chengtivirus
Genus Crustavirus
Genus Wastrivirus
Class Yunchangviricetes
Order Goujianvirales
Family Yueviridae
Subphylum Polyploviricotina
Class Ellioviricetes
Order Bunyavirales
Family Arenaviridae – includes Lassa virus
Family Feraviridae
Family Fimoviridae
Family Hantaviridae
Family Jonviridae
Family Nairoviridae
Family Peribunyaviridae
Family Phasmaviridae
Family Phenuiviridae
Family Tospoviridae
Class Insthoviricetes
Order Articulavirales
Family Amnoonviridae—includes Taastrup virus
Family Orthomyxoviridae—includes Influenza viruses
Unassigned genera:
Genus Deltavirus – includes Hepatitis D virus
Host range
Viruses of the families Arenaviridae, Orthomyxoviridae, Paramyxoviridae, and Pneumoviridae are able to infect vertebrates. Viruses of the families Bunyaviridae and Rhabdoviridae are able to infect vertebrates, arthropods, and plants. Viruses of the genus Tenuivirus only infect plants. A few viruses known to infect humans include Marburg virus, Ebola, measles, mumps, rabies, and influenza.

Lassa virus (Arenaviridae)

Lymphocytic choriomeningitis virus (Arenaviridae)

Hantavirus (Bunyaviridae)

Marburg Virus (Filoviridae)

Ebola virus (Filoviridae)

Influenza (Orthomyxoviridae)

Measles (Paramyxoviridae)

Mumps virus (Paramyxoviridae)

Human respiratory syncytial virus (Paramyxoviridae)

Parainfluenza (Paramyxoviridae)

Rabies (Rhabdoviridae)

Vesicular stomatitis virus (Rhabdoviridae)

Genome
The genome for negative-stranded RNA virus (NSV) consists of one to several single-stranded RNAs, which are assembled into complexes.[9] These complexes function as templates for the transcription and replication of the NSV genome by RNA polymerase. The NSV genome has been observed as being either segmented and nonsegmented.[9] The segmented genome can be divided up into anywhere between 2–8 RNA molecules.[9] A distinctive feature of the NSV genome is its highly structured organization. Multiple monomers of either the ribonucleoprotein (RNP) complexes or nucleocapsids associate with the RNA to create these organized complexes.[9] Nonsegmented RNA follows a sequential pattern of gene expression.[9] With segmented RNA, each individual segment is contained in a distinct RNP complex.[9] These complexes function independently for transcription and replication related processes.[9]

NSV ribonucleoproteins (RNPs) generally adopt a helical conformation.[9] For nonsegmented NSVs, these conformations are typically linear in fashion, and are relatively rigid.[10][11] Segmented NSVs are present in a more flexible, circular conformation.[12] This results from non-covalent RNA-RNA interactions between the 5’- and 3’-termini of the RNA segments.[13] Regarding the helical character of NSV RNPs, the main determinant of this conformation is the NP/N protein.[9] The structure of virion full-length RNPs are typically presented as a left-handed, double-helical arrangement of two NP strands that are opposite in polarity.[9] Recombinant RNPs have a different structure, generally consisting of a right-handed helix.[14] Nevertheless, wild type RNPs isolated from virus present left-handed helix [15]

Catalytic activity related to RNA synthesis is associated with a very large protein, termed the L protein. This is a multi-enzymatic polypeptide that is responsible for multiple tasks. These activities span multiple domains, including mRNA synthesis/modification and the formation of ribonucleoproteins.[16][17] Through phylogenetic analysis, it was determined that NSV RNA polymerases share a common ancestor with other RNA polymerases from various origins.[9] This is further supported by various L proteins displaying highly conserved sequence blocks that are in series, yet separated by variable regions.[18]

When discussing the NSV RNP, the NP/N protein is considered to be the most abundant element of the ribonucleoprotein.[9] These elements are what provide the basis for the RNPs helical conformation.[9] NP/N proteins are also vital for the transcription and replication of full-length RNA templates.[9] The proper function of NP/N proteins rely on their capacity to oligomerize. This defines the ability of NP/N proteins to complex together to form larger structural elements. The oligomerization mechanism is unique between the nonsegmented NSV genome (nsNSV) and segmented NSV genome (sNSV).[9] For nsNSVs, interactions occur between the protein monomers, while the stabilization of this complex occurs through inter-monomeric contact involving N-terminal and/or C-terminal protein extensions.[11][19][20] This contributes to the viral RNP helical structure.[10][11][21] Oligomerization for sNSVs has been shown to be similar to this for some Bunyaviridae, but it may also take place much more flexibly, defined by their ability to form much smaller oligomers.[22][9] These include, but are not limited to, dimers, trimers, tetramers, long helices, and more complex structures.[9]

NSV Life Cycle and Replication
Negative-strand RNA viruses (NSV) can be classified into 21 distinct families. The families consisting of nonsegmented genomes include Rhabdo-, Paramyxo-, Filo- and Borna-. Orthomyxo-, Bunya-, Arenaviridae- contain genomes of six to eight, three, or two negative-sense RNA segments, respectively.[23] Many highly prevalent human pathogens such as the respiratory syncytial virus (RSV), parainfluenza viruses, influenza viruses, Ebola virus, Marburg virus are included within the NSV. The life cycle of NSV has a number of steps. The virus first infects the host cell by binding to the host cell receptor through a viral surface glycoprotein.[24] The fusion of the glycoprotein viral membrane with the plasma membrane of the host cell in an acidic environment allows for the release of viral ribonucleoprotein (RNP) complexes into the cytoplasm. Most NSV replicate in the cytoplasm of infected cells. Newly synthesized RNP complexes are assembled with viral structural proteins at the plasma membrane or at membranes of the Golgi apparatus.[23] This is all followed by the release of the newly synthesized viruses.

In regards to the replication and transcription of non-segmented NSV, the genes of these NSV are made up of three regulatory regions: a gene end signal, an intergenic region, and a gene start signal.[23][25] One example of gene end signals are in a specific virus called the vesicular stomatitis virus (VSV) contains gene end signals that are highly conservative. The intergenic region is highly variable and consists of conserved dinucleotide, trinucleotide, or regions of up to 143 nucleotides.[25] The various lengths of the intergenic regions correlate with transcriptional attenuation, however diverse intergenic regions do not alter the gene expression. The gene start signals are highly specific as the first three nucleotides are critical for the gene expression.[23][25][26]

Molecular Mechanisms of Innate Antiviral Immune Inhibition
A cell’s innate immune response is the first line of defense for finding viral infections. The innate immune response triggers the production of type I interferons (IFN) and pro-inflammatory cytokines.[27][28] However, non-segmented negative sense RNA viruses (NNSV) have developed multifunctional proteins that can diffuse this innate response pathway to avoid antiviral functions within the cell.[28] This mainly occurs through the NNSV's proteins interacting with other cellular proteins involved in the type I interferon signaling pathway.[27] Due to the expansive nature of the immune pathway, NNSVs have a variety of areas throughout the signaling cascade that can be targeted for interruption of the production of type I interferons or pro-inflammatory cytokines.[29] Such areas include inhibiting the induction of the IFN pathway or inhibiting the response from the IFN signaling cascade.

NNSV-Mediated Inhibition of IFN Induction
NNSVs target several induction pathway areas, as outlined in the image, to avoid detection within the cell, or even inhibit that specific area of the signaling cascade. One such example of NNSVs avoiding cellular detection arises with mutations, which sequester the pathogen-associated molecular pathways.[27][30] By creating a mutation within the nucleotide sequence, specifically ones important for binding double stranded DNA or other proteins, the virus is able to go undetected by cell, avoid activation of the cellular antiviral response, and evade the immune response.

NNSVs can also bind to cellular receptors throughout the pro-inflammatory cytokine pathway to inhibit the immune response.[27] By carrying accessory proteins that directly bind to pattern recognition receptors, the virus can use its accessory proteins to induce conformational changes throughout other immune response proteins and inhibit cellular responses.[29] Generally, the pattern recognition receptors detect infection-associated molecules commonly associated with viruses, but some viruses carry accessory proteins that reconfigure the protein to inhibit its function and block the rest of the signaling cascade that would produce an immune response.

Other areas of inhibition of induction apply similar concepts of binding to cellular proteins and inhibiting their function throughout the immune cascade.[27][28] These include binding to proteins involved in dephosphorylation pathways and blocking DNA binding transcription factors. In each case, the accessory proteins coded for in the nucleotide sequence inhibit a critical function of other innate cellular proteins, disrupting the signaling cascade for producing type I interferons and pro-inflammatory cytokines.

NNSV-Mediated Inhibition of IFN Response
Another way that NSVs avoid the host immune response is to encode for proteins that target the JAK/STAT pathway or the nuclear transports mechanisms for transcription factors. Each of these are a portion of the IFN pathway described previously in the immune system’s innate response to viral infection.

JAK/STAT pathway
For the JAK/STAT pathway depicted in the image, a critical reaction for inducing the pathway is the proper phosphorylation of the TYK2 and JAK1 proteins.[27] Upon phosphorylation, the rest of the STAT pathway will begin and lead to the production of antiviral genes.[31] NNSVs have the capability to synthesize proteins that target the phosphorylation step of the pathway. By preventing the phosphorylation of TYK2 and JAK1, they stop the IFNα/β pathway and bring the antiviral immune response to a halt.[32] Similarly, viruses can also synthesize proteins that prevent the phosphorylation of STAT1 a little further along the signaling cascade. This process halts the IFNα/β pathway, just like preventing phosphorylation of TYK2 and JAK1.

Further down the IFNα/β pathway, STAT1 and STAT2 are transported across the nuclear membrane, as depicted in the image.[27][32] They accordingly bind to the DNA sequence and behave as transcription factors- affecting the level of gene production throughout the cell. In normal cellular function, this pathway will behave normally in response to viral infection, leading to the production of antiviral genes and the induction of an immune response.[27] However, NNSVs have developed the capability to generate complexes that target the protein responsible for translocating STAT1 across the nuclear membrane. By binding to and inhibiting this function, STAT1 is never able to bind to the DNA and properly regulate the production of antiviral genes.[31][32] This pathway of inhibiting the IFN response helps the NNSV go undetected within the cell and avoid certain immune response pathways.

Ubiquitination
Another important process used throughout many cellular processes is ubiquitination—which is outlined in the image below. Many cells use this to locate and identify viruses, and to restrict the viral infection.[33] NNSVs however have developed a pathway to synthesize proteins that target the ubiquitin pathway along many of the signaling cascades descriptive of the IFN response. More specifically, the NNSVs are capable of reprogramming the host cell’s ubiquitination pathway in such a way that leads to the degradation of host cell mechanism that would otherwise silence a viral infection.[34]

Ubiquitination Pathway
Common Mechanism for RNA Encapsidation by NSVs
Like all viruses, negative-sense RNA viruses (NSVs) contain a protein capsid that encapsulates the genomic material. The nucleocapsid of NSVs is assembled with a single nucleocapsid protein, and the viral RNA. Each NSV nucleocapsid is packaged inside a lipid envelope, but the appearance of the nucleocapsid differs from virus to virus.[35] For example, in rhabdoviruses, the nucleocapsid assumes a bullet shape,[21] while in paramyxoviruses, the nucleocapsid is filamentous or herringbone-like.[36] However, when the nucleocapsids are released from the virion, they all appear like a coil.[35]

So far, the atomic structures of nucleocapsid-like-particles (NLP) have been elucidated for three NSV families: Rhabdoviridae, Paramyxoviridae, and Bunyaviridae. One important element of NSVs is that the capsid protein (N) is first synthesized as a monomeric protein (N0). N0 is a capsid protein that assembles a capsid to accommodate any RNA sequence. N0 is kept monomeric in different ways depending on which family of NSVs a virus falls into. For instance, rhabdoviruses keep the N0 monomeric by forming a complex with the phosphoprotein (P).[21] It has been found that both the N- and C terminal regions of P bind to the capsid protein. Essentially, the P binding occupies the site required for N0 oligomerization. Other viruses, such as bunyaviruses, simply sequester the N terminus by N itself. Nonetheless, it is essential for N to be monomeric for the NSV to be competent in encapsidating viral RNA.[21]

In terms of the structure of the nucleocapsid, the N protein will eventually oligomerize to encapsidate the single-stranded RNA. In some NSVs the N subunits are oriented in a parallel orientation, and the ssRNA is sequestered in the center. In most NSVs, the nucleocapsid appears to be a random coil, and the symmetry is linear.[37] Because the N subunits are oriented in a parallel fashion, the cross-molecular interactions among the subunits stabilize the nucleocapsid and are critical for capsid formation. The linear interactions along the encapsidated single-stranded RNA are actually a unique feature to NSVs.[21] X-ray crystal structures of N proteins and EM micrographs of RNP complexes from a number of Bunyaviridae (a Family of segmented NSVs that includes the Bunyamwera virus and the Schmallenberg virus) show that in these viruses the nucleocapsid adopts a helical arrangement where the N proteins form a head-to-tail chain by linking to each other via a flexible N-terminal arm. The resulting chain forms tight coils with four N proteins per turn that holds the circular ssRNA of these viruses on the inside of the coils and extend to form large circular filaments.[22]

Structure of a Nucleocaspid
The process of encapsidation is a concomitant process with viral replication, likely at the site of the viral RNA replication process.[38] Another unique feature of NSVs is that the sequestered bases are stacked to form a motif similar to half of the A-form double helix of RNA. The stacking arrangement allows for maximized packaging of the RNA in the capsid.[21] The base stacking may actually contribute to the overall stability of the nucleocapsid, and is dependent on the RNA sequence (i.e. poly(rA) is the most stable).[39] An interesting finding is that specific sequences in the sequestered RNA genome may regulate viral functions. For translational termination, there is a U7 track at the end of each coding region, causing this to be the least stable region. This therefore promotes dissociation of the transcription complex.[21] A unique aspect of NSVs is the conserved (3H+5H) motif, which has been identified to constitute the RNA cavity through secondary structure elements of the N protein.[40]

Lastly, a main distinction between NSVs from other viruses is that the nucleocapsid actually serves as the template for viral RNA synthesis. During synthesis, the nucleocapsid undergoes a conformational change to release the RNA template. After transcription is complete, the RNA is repositioned in the cavity, and the nucleocapsid is restored.[21]

A retrovirus is a type of RNA virus that inserts a copy of its genome into the DNA of a host cell that it invades, thus changing the genome of that cell.[2]

Once inside the host cell's cytoplasm, the virus uses its own reverse transcriptase enzyme to produce DNA from its RNA genome, the reverse of the usual pattern, thus retro (backwards). The new DNA is then incorporated into the host cell genome by an integrase enzyme, at which point the retroviral DNA is referred to as a provirus. The host cell then treats the viral DNA as part of its own genome, transcribing and translating the viral genes along with the cell's own genes, producing the proteins required to assemble new copies of the virus. It is difficult to detect the virus until it has infected the host. At that point, the infection will persist indefinitely.

In most viruses, DNA is transcribed into RNA, and then RNA is translated into protein. However, retroviruses function differently, as their RNA is reverse-transcribed into DNA, which is integrated into the host cell's genome (when it becomes a provirus), and then undergoes the usual transcription and translational processes to express the genes carried by the virus. The information contained in a retroviral gene is thus used to generate the corresponding protein via the sequence: RNA → DNA → RNA → polypeptide. This extends the fundamental process identified by Francis Crick (one gene-one peptide) in which the sequence is DNA → RNA → peptide (proteins are made of one or more polypeptide chains; for example, haemoglobin is a four-chain peptide).

Retroviruses are valuable research tools in molecular biology, and they have been used successfully in gene delivery systems.[3]

Contents
1 Structure
2 Multiplication
3 Transmission
4 Provirus
5 Early evolution
6 Gene therapy
7 Cancer
8 Classification
8.1 Exogenous
8.1.1 Group VI viruses
8.1.2 Group VII viruses
8.2 Endogenous
9 Treatment
10 Treatment of veterinary retroviruses
11 References
12 External links
Structure
Virions of retroviruses consist of enveloped particles about 100 nm in diameter. The virions also contain two identical single-stranded RNA molecules 7–10 kilobases in length. Although virions of different retroviruses do not have the same morphology or biology, all the virion components are very similar.[4]

The main virion components are:

Envelope: composed of lipids (obtained from the host plasma membrane during the budding process) as well as glycoprotein encoded by the env gene. The retroviral envelope serves three distinct functions: protection from the extracellular environment via the lipid bilayer, enabling the retrovirus to enter/exit host cells through endosomal membrane trafficking, and the ability to directly enter cells by fusing with their membranes.
RNA: consists of a dimer RNA. It has a cap at the 5' end and a poly(A) tail at the 3' end. The RNA genome also has terminal noncoding regions, which are important in replication, and internal regions that encode virion proteins for gene expression. The 5' end includes four regions, which are R, U5, PBS, and L. The R region is a short repeated sequence at each end of the genome used during the reverse transcription to ensure correct end-to-end transfer in the growing chain. U5, on the other hand, is a short unique sequence between R and PBS. PBS (primer binding site) consists of 18 bases complementary to 3' end of tRNA primer. L region is an untranslated leader region that gives the signal for packaging of the genome RNA. The 3' end includes 3 regions, which are PPT (polypurine tract), U3, and R. The PPT is a primer for plus-strand DNA synthesis during reverse transcription. U3 is a sequence between PPT and R, which serves as a signal that the provirus can use in transcription. R is the terminal repeated sequence at 3' end.
Proteins: consisting of gag proteins, protease (PR), pol proteins, and env proteins.
Group-specific antigen (gag) proteins are major components of the viral capsid, which are about 2000–4000 copies per virion.
Protease is expressed differently in different viruses. It functions in proteolytic cleavages during virion maturation to make mature gag and pol proteins.
Pol proteins are responsible for synthesis of viral DNA and integration into host DNA after infection.
Env proteins play a role in association and entry of virions into the host cell.[5] Possessing a functional copy of an env gene is what makes retroviruses distinct from retroelements.[6] The ability of the retrovirus to bind to its target host cell using specific cell-surface receptors is given by the surface component (SU) of the Env protein, while the ability of the retrovirus to enter the cell via membrane fusion is imparted by the membrane-anchored trans-membrane component (TM). Thus it is the Env protein that enables the retrovirus to be infectious.
Multiplication

A retrovirus has a membrane containing glycoproteins, which are able to bind to a receptor protein on a host cell. There are two strands of RNA within the cell that have three enzymes: protease, reverse transcriptase, and integrase (1). The first step of replication is the binding of the glycoprotein to the receptor protein (2). Once these have been bound, the cell membrane degrades, becoming part of the host cell, and the RNA strands and enzymes enter the cell (3). Within the cell, reverse transcriptase creates a complementary strand of DNA from the retrovirus RNA and the RNA is degraded; this strand of DNA is known as cDNA (4). The cDNA is then replicated, and the two strands form a weak bond and enter the nucleus (5). Once in the nucleus, the DNA is integrated into the host cell's DNA with the help of integrase (6). This cell can either stay dormant, or RNA may be synthesized from the DNA and used to create the proteins for a new retrovirus (7). Ribosome units are used to translate the mRNA of the virus into the amino acid sequences which can be made into proteins in the rough endoplasmic reticulum. This step will also make viral enzymes and capsid proteins (8). Viral RNA will be made in the nucleus. These pieces are then gathered together and are pinched off of the cell membrane as a new retrovirus (9).
When retroviruses have integrated their own genome into the germ line, their genome is passed on to a following generation. These endogenous retroviruses (ERVs), contrasted with exogenous ones, now make up 5–8% of the human genome.[7] Most insertions have no known function and are often referred to as “junk DNA”. However, many endogenous retroviruses play important roles in host biology, such as control of gene transcription, cell fusion during placental development in the course of the germination of an embryo, and resistance to exogenous retroviral infection. Endogenous retroviruses have also received special attention in the research of immunology-related pathologies, such as autoimmune diseases like multiple sclerosis, although endogenous retroviruses have not yet been proven to play any causal role in this class of disease.[8]

While transcription was classically thought to occur only from DNA to RNA, reverse transcriptase transcribes RNA into DNA. The term “retro” in retrovirus refers to this reversal (making DNA from RNA) of the usual direction of transcription. It still obeys the central dogma of molecular biology, which states that information can be transferred from nucleic acid to nucleic acid but cannot be transferred back from protein to either protein or nucleic acid. Reverse transcriptase activity outside of retroviruses has been found in almost all eukaryotes, enabling the generation and insertion of new copies of retrotransposons into the host genome. These inserts are transcribed by enzymes of the host into new RNA molecules that enter the cytosol. Next, some of these RNA molecules are translated into viral proteins. For example, the gag gene is translated into molecules of the capsid protein, the pol gene is translated into molecules of reverse transcriptase, and the env gene is translated into molecules of the envelope protein. It is important to note that a retrovirus must “bring” its own reverse transcriptase in its capsid, otherwise it is unable to utilize the enzymes of the infected cell to carry out the task, due to the unusual nature of producing DNA from RNA.

Industrial drugs that are designed as protease and reverse-transcriptase inhibitors are made such that they target specific sites and sequences within their respective enzymes. However these drugs can quickly become ineffective due to the fact that the gene sequences that code for the protease and the reverse transcriptase quickly mutate. These changes in bases cause specific codons and sites with the enzymes to change and thereby avoid drug targeting by losing the sites that the drug actually targets.

Because reverse transcription lacks the usual proofreading of DNA replication, a retrovirus mutates very often. This enables the virus to grow resistant to antiviral pharmaceuticals quickly, and impedes the development of effective vaccines and inhibitors for the retrovirus.[9]

One difficulty faced with some retroviruses, such as the Moloney retrovirus, involves the requirement for cells to be actively dividing for transduction. As a result, cells such as neurons are very resistant to infection and transduction by retroviruses. This gives rise to a concern that insertional mutagenesis due to integration into the host genome might lead to cancer or leukemia. This is unlike Lentivirus, a genus of Retroviridae, which are able to integrate their RNA into the genome of non-dividing host cells.

Transmission
Cell-to-cell[10]
Fluids
Airborne, like the Jaagsiekte sheep retrovirus.
Provirus
This DNA can be incorporated into host genome as a provirus that can be passed on to progeny cells. The retrovirus DNA is inserted at random into the host genome. Because of this, it can be inserted into oncogenes. In this way some retroviruses can convert normal cells into cancer cells. Some provirus remains latent in the cell for a long period of time before it is activated by the change in cell environment.

Early evolution
Studies of retroviruses led to the first demonstrated synthesis of DNA from RNA templates, a fundamental mode for transferring genetic material that occurs in both eukaryotes and prokaryotes. It has been speculated that the RNA to DNA transcription processes used by retroviruses may have first caused DNA to be used as genetic material. In this model, the RNA world hypothesis, cellular organisms adopted the more chemically stable DNA when retroviruses evolved to create DNA from the RNA templates.

An estimate of the date of evolution of the foamy-like endogenous retroviruses placed the time of the most recent common ancestor at > 450 million years ago.[11]

Gene therapy
Gammaretroviral and lentiviral vectors for gene therapy have been developed that mediate stable genetic modification of treated cells by chromosomal integration of the transferred vector genomes. This technology is of use, not only for research purposes, but also for clinical gene therapy aiming at the long-term correction of genetic defects, e.g., in stem and progenitor cells. Retroviral vector particles with tropism for various target cells have been designed. Gammaretroviral and lentiviral vectors have so far been used in more than 300 clinical trials, addressing treatment options for various diseases.[3][12] Retroviral mutations can be developed to make transgenic mouse models to study various cancers and their metastatic models.

Cancer
Retroviruses that cause tumor growth include Rous sarcoma virus and Mouse mammary tumor virus. Cancer can be triggered by proto-oncogenes that were mistakenly incorporated into proviral DNA or by the disruption of cellular proto-oncogenes. Rous sarcoma virus contains the src gene that triggers tumor formation. Later it was found that a similar gene in cells is involved in cell signaling, which was most likely excised with the proviral DNA. Nontransforming viruses can randomly insert their DNA into proto-oncogenes, disrupting the expression of proteins that regulate the cell cycle. The promoter of the provirus DNA can also cause over expression of regulatory genes.

Classification

Phylogeny of Retroviruses
Exogenous
These are infectious RNA- or DNA-containing viruses which are transmitted from individual to individual.

Reverse-transcribing viruses fall into 2 groups of the Baltimore classification.[clarification needed][citation needed]

Group VI viruses
All members of Group VI use virally encoded reverse transcriptase, an RNA-dependent DNA polymerase, to produce DNA from the initial virion RNA genome. This DNA is often integrated into the host genome, as in the case of retroviruses and pseudoviruses, where it is replicated and transcribed by the host.

Group VI includes:

Order Ortervirales
Family Belpaoviridae
Family Metaviridae
Family Pseudoviridae
Family Retroviridae – Retroviruses, e.g. HIV
Family Caulimoviridae – a VII group virus family (see below)
The family Retroviridae was previously divided into three subfamilies (Oncovirinae, Lentivirinae, and Spumavirinae), but are now divided into two: Orthoretrovirinae and Spumaretrovirinae. The term oncovirus is now commonly used to describe a cancer-causing virus. This family now includes the following genera:

Subfamily Orthoretrovirinae:
Genus Alpharetrovirus; type species: Avian leukosis virus; others include Rous sarcoma virus
Genus Betaretrovirus; type species: Mouse mammary tumour virus
Genus Gammaretrovirus; type species: Murine leukemia virus; others include Feline leukemia virus
Genus Deltaretrovirus; type species: Bovine leukemia virus; others include the cancer-causing Human T-lymphotropic virus
Genus Epsilonretrovirus; type species: Walleye dermal sarcoma virus
Genus Lentivirus; type species: Human immunodeficiency virus 1; others include Simian, Feline immunodeficiency viruses
Subfamily Spumaretrovirinae:
Genus Bovispumavirus; type species: Bovine foamy virus
Genus Equispumavirus; type species: Equine foamy virus
Genus Felispumavirus; type species: Feline foamy virus
Genus Prosimiispumavirus; type species: Brown greater galago prosimian foamy virus
Genus Simiispumavirus; type species: Eastern chimpanzee simian foamy virus
Note that according to ICTV 2017, genus Spumavirus has been divided into five genera, and its former type species Simian foamy virus is now upgraded to genus Simiispumavirus with not less than 14 species, including new type species Eastern chimpanzee simian foamy virus.[13]

Group VII viruses
Both families in Group VII have DNA genomes contained within the invading virus particles. The DNA genome is transcribed into both mRNA, for use as a transcript in protein synthesis, and pre-genomic RNA, for use as the template during genome replication. Virally encoded reverse transcriptase uses the pre-genomic RNA as a template for the creation of genomic DNA.

Group VII includes:

Family Caulimoviridae – e.g. Cauliflower mosaic virus
Family Hepadnaviridae – e.g. Hepatitis B virus
The latter family is closely related to the newly proposed

Family Nackednaviridae – e.g. African cichlid nackednavirus (ACNDV), formerly named African cichlid hepatitis B virus (ACHBV).[14]
whilst families Belpaoviridae, Metaviridae, Pseudoviridae, Retroviridae, and Caulimoviridae constitute the order Ortervirales.[15]

Endogenous
Main article: Endogenous retrovirus
Endogenous retroviruses are not formally included in this classification system, and are broadly classified into three classes, on the basis of relatedness to exogenous genera:

Class I are most similar to the gammaretroviruses
Class II are most similar to the betaretroviruses and alpharetroviruses
Class III are most similar to the spumaviruses.
Treatment
Antiretroviral drugs are medications for the treatment of infection by retroviruses, primarily HIV. Different classes of antiretroviral drugs act on different stages of the HIV life cycle. Combination of several (typically three or four) antiretroviral drugs is known as highly active anti-retroviral therapy (HAART).[16]

Treatment of veterinary retroviruses
Feline leukemia virus and Feline immunodeficiency virus infections are treated with biologics, including the only immunomodulator currently licensed for sale in the United States, Lymphocyte T-Cell Immune Modulator (LTCI).[17]

dsDNA-RT viruses are the seventh group in the Baltimore virus classification. They are not considered DNA viruses (class I of Baltimore classification), but rather reverse transcribing viruses because they replicate through an RNA intermediate. It includes the families Hepadnaviridae and Caulimoviridae.

The term “pararetrovirus” is also used for this group.[1] The term was introduced in 1985.[2]

II. (+)ssDNA
Rodzina: Parvoviridae – parwowirusy (najmniejsze znane wirusy)
- Parvovirus – wirus rumienia zakaźnego („choroby piątej”)
III. dsRNA
Rodzina: Reoviridae – reowirusy
- Rotavirus – rotawirus (wirus ostrej biegunki niemowląt i dzieci)
IV. (+)ssRNA
Rodzina: Togaviridae – togawirusy
- Rubivirs – wirus różyczki
Rodzina: Flaviviridae – flawiwirusy
- Hepacivirus – wirus zapalenia wątroby typu C
- Flavivirus – flawiwirus (w tym wirus dengi, wirus żółtej febry)
Rodzina: Picornaviridae – pikornawirusy
- Hepatovirus – wirus zapalenia wątroby typu A
Rodzina: Potyviridae – potywirusy
- Potyvirus – TBV, wirus pstrości kwiatów tulipana
V. (−)ssRNA
Rodzina: Orthomyxoviridae – ortomyksowirusy
- Influenzavirus – wirus grypy
Rodzina: Paramyxoviridae – paramyksowirusy
- Paramyxovirus – wirus paragrypy; wirus świnki
- Morbilivirus – wirus odry
VI. (+)ssRNA-RT
Rodzina: Retroviridae – retrowirusy
- Lentivirus – wirus HIV
VII. dsDNA-RT
Rodzina: Hepadnaviridae – hepadnawirusy
- Orthohepadnavirus – wirus zapalenia wątroby typu B

 Satellite viruses encode structural proteinsrequired for the formation of infectious particles butdepend on helper viruses for completing their replicationcycles. Because of this unique property, satellite virusesthat infect plants, arthropods, or mammals, as well as themore recently discovered satellite-like viruses that infectprotists (virophages), have been grouped with other, so-called ‘‘sub-viral agents.” For the most part, satelliteviruses are therefore not classified. We argue thatpossession of a coat-protein-encoding gene and the abilityto form virions are the defining features of abona fidevirus. Accordingly, all satellite viruses and virophagesshould be consistently classified within appropriate taxa.We propose to create four new genera —Albetovirus,Aumaivirus,Papanivirus, andVirtovirus— for positive-sense single-stranded (?) RNA satellite viruses that infectplants and the familySarthroviridae, including the genusMacronovirus, for (?)RNA satellite viruses that infectarthopods. For double-stranded DNA virophages, we pro-pose to establish the familyLavidaviridae, including twogenera,SputnikvirusandMavirus.

Viroids are the smallest infectious pathogens known. They are composed solely of a short strand of circular, single-stranded RNA that has no protein coating. All known viroids are inhabitants of higher plants, in which most cause diseases, ranging in economic importance.

Discovery of the viroid triggered the third major extension of the biosphere in history to include smaller lifelike entities—after the discovery of the “subvisible” microorganisms by Antonie van Leeuwenhoek in 1675 and the “submicroscopic” viruses by Dmitri Iosifovich Ivanovsky in 1892.

The unique properties of viroids have been recognized by the International Committee for Virus Taxonomy with the creation of a new order of subviral agents.[1]

The first recognized viroid, the pathogenic agent of the potato spindle tuber disease, was discovered, initially molecularly characterized, and named by Theodor Otto Diener, plant pathologist at the U.S Department of Agriculture's Research Center in Beltsville, Maryland, in 1971.[2][3] This viroid is now called Potato spindle tuber viroid, abbreviated PSTVd.

In a year 2000 compilation of the most important Millennial Milestones in Plant Pathology, the American Phytopathological Society has ranked the 1971 discovery of the viroid as one of the Millennium's ten most important pathogen discoveries.[4]

As cogently expressed by Flores et al: Viruses (and viroids) share the most characteristic property of living beings: In an appropriate environment, they are able to generate copies of themselves, in other words, they are endowed with autonomous replication (and evolution). It is in this framework where viroids represent the frontier of life (246 to 467nt), an aspect that should attract the attention of anybody interested in biology.[5]

Although viroids are composed of nucleic acid, they do not code for any protein.[6][7] The viroid's replication mechanism uses RNA polymerase II, a host cell enzyme normally associated with synthesis of messenger RNA from DNA, which instead catalyzes “rolling circle” synthesis of new RNA using the viroid's RNA as a template. Some viroids are ribozymes, having catalytic properties that allow self-cleavage and ligation of unit-size genomes from larger replication intermediates.[8]

With Diener's 1989 hypothesis[9] that viroids may represent “living relics” from the widely assumed, ancient, and non-cellular RNA world—extant before the evolution of DNA or proteins—viroids have assumed significance beyond plant pathology to evolutionary science, by representing the most plausible RNAs capable of performing crucial steps in abiogenesis, the evolution of life from inanimate matter.

The human pathogen hepatitis D virus is a “defective” RNA virus similar to a viroid.[10]

Contents
1 Taxonomy
2 Transmission
3 Replication
4 RNA silencing
5 RNA world hypothesis
6 History
7 See also
8 References
9 External links
Taxonomy
Family Pospiviroidae
Genus Pospiviroid; type species: Potato spindle tuber viroid; 356–361 nucleotides(nt)[11]
Genus Pospiviroid; another species: Citrus exocortis viroid; 368–467 nt[11]
Genus Hostuviroid; type species: Hop stunt viroid; 294–303 nt[11]
Genus Cocadviroid; type species: Coconut cadang-cadang viroid; 246–247 nt[11]
Genus Apscaviroid; type species: Apple scar skin viroid; 329–334 nt[11]
Genus Coleviroid; type species: Coleus blumei viroid 1; 248–251 nt[11]

Putative secondary structure of the PSTVd viroid. The highlighted nucleotides are found in most other viroids.
Family Avsunviroidae
Genus Avsunviroid; type species: Avocado sunblotch viroid; 246–251 nt[11]
Genus Pelamoviroid; type species: Peach latent mosaic viroid; 335–351 nt[11]
Genus Elaviroid; type species: Eggplant latent viroid; 332–335 nt[11]
Transmission

The reproduction mechanism of a typical viroid. Leaf contact transmits the viroid. The viroid enters the cell via its plasmodesmata. RNA polymerase II catalyzes rolling-circle synthesis of new viroids.
Viroid infections can be transmitted by aphids, by cross contamination following mechanical damage to plants as a result of horticultural or agricultural practices, or from plant to plant by leaf contact.[11][12]

Replication
Viroids replicate in the nucleus (Pospiviroidae) or chloroplasts (Avsunviroidae) of plant cells in three steps through an RNA-based mechanism. They require RNA polymerase II, a host cell enzyme normally associated with synthesis of messenger RNA from DNA, which instead catalyzes “rolling circle” synthesis of new RNA using the viroid as template.[13][14]

RNA silencing
There has long been uncertainty over how viroids induce symptoms in plants without encoding any protein products within their sequences. Evidence suggests that RNA silencing is involved in the process. First, changes to the viroid genome can dramatically alter its virulence.[15] This reflects the fact that any siRNAs produced would have less complementary base pairing with target messenger RNA. Secondly, siRNAs corresponding to sequences from viroid genomes have been isolated from infected plants. Finally, transgenic expression of the noninfectious hpRNA of potato spindle tuber viroid develops all the corresponding viroid-like symptoms.[16] This indicates that when viroids replicate via a double stranded intermediate RNA, they are targeted by a dicer enzyme and cleaved into siRNAs that are then loaded onto the RNA-induced silencing complex. The viroid siRNAs contain sequences capable of complementary base pairing with the plant's own messenger RNAs, and induction of degradation or inhibition of translation causes the classic viroid symptoms.[17]

RNA world hypothesis
Diener's 1989 hypothesis[18] had proposed that the unique properties of viroids make them more plausible macromolecules than introns, or other RNAs considered in the past as possible “living relics” of a hypothetical, pre-cellular RNA world. If so, viroids have assumed significance beyond plant virology for evolutionary theory, because their properties make them more plausible candidates than other RNAs to perform crucial steps in the evolution of life from inanimate matter (abiogenesis). Diener's hypothesis was mostly forgotten until 2014, when it was resurrected in a review article by Flores et al.,[19] in which the authors summarized Diener's evidence supporting his hypothesis as:

Viroids' small size, imposed by error-prone replication.
Their high guanine and cytosine content, which increases stability and replication fidelity.
Their circular structure, which assures complete replication without genomic tags.
Existence of structural periodicity, which permits modular assembly into enlarged genomes.
Their lack of protein-coding ability, consistent with a ribosome-free habitat.
Replication mediated in some by ribozymes—the fingerprint of the RNA world.
The presence, in extant cells, of RNAs with molecular properties predicted for RNAs of the RNA World constitutes another powerful argument supporting the RNA World hypothesis.

History
In the 1920s, symptoms of a previously unknown potato disease were noticed in New York and New Jersey fields. Because tubers on affected plants become elongated and misshapen, they named it the potato spindle tuber disease.[20]

The symptoms appeared on plants onto which pieces from affected plants had been budded—indicating that the disease was caused by a transmissible pathogenic agent. A fungus or bacterium could not be found consistently associated with symptom-bearing plants, however, and therefore, it was assumed the disease was caused by a virus. Despite numerous attempts over the years to isolate and purify the assumed virus, using increasingly sophisticated methods, these were unsuccessful when applied to extracts from potato spindle tuber disease-afflicted plants.[3]

In 1971 Theodor O. Diener showed that the agent was not a virus, but a totally unexpected novel type of pathogen, 1/80th the size of typical viruses, for which he proposed the term “viroid”.[2] Parallel to agriculture-directed studies, more basic scientific research elucidated many of viroids' physical, chemical, and macromolecular properties. Viroids were shown to consist of short stretches (a few hundred nucleobases) of single-stranded RNA and, unlike viruses, did not have a protein coat. Compared with other infectious plant pathogens, viroids are extremely small in size, ranging from 246 to 467 nucleobases; they thus consist of fewer than 10,000 atoms. In comparison, the genomes of the smallest known viruses capable of causing an infection by themselves are around 2,000 nucleobases long.[21]

In 1976, Sänger et al.[22] presented evidence that potato spindle tuber viroid is a “single-stranded, covalently closed, circular RNA molecule, existing as a highly base-paired rod-like structure”—believed to be the first such molecule described. Circular RNA, unlike linear RNA, forms a covalently closed continuous loop, in which the 3' and 5' ends present in linear RNA molecules have been joined together. Sänger et al. also provided evidence for the true circularity of viroids by finding that the RNA could not be phosphorylated at the 5' terminus. Then, in other tests, they failed to find even one free 3' end, which ruled out the possibility of the molecule having two 3' ends. Viroids thus are true circular RNAs.

The single-strandedness and circularity of viroids was confirmed by electron microscopy,[23] and Gross et al. determined the complete nucleotide sequence of potato spindle tuber viroid in 1978.[24] PSTVd was the first pathogen of a eukaryotic organism for which the complete molecular structure has been established. Over thirty plant diseases have since been identified as viroid-, not virus-caused, as had been assumed.[21][25]

In 2014, New York Times science writer Carl Zimmer published a popularized piece that mistakenly credited Flores et al. with the hypothesis' original conception.

 

Virusoids are circular single-stranded RNA(s) dependent on viruses for replication and encapsidation.[1] The genome of virusoids consist of several hundred nucleotides and does not code for any proteins. In humans, the hepatitis D virus is a virusoid capable of causing pathology when in the presence of the hepatitis B virus.

Virusoids are essentially viroids that have been encapsulated by a helper virus coat protein. They are thus similar to viroids in their means of replication (rolling circle replication) and due to the lack of genes, but they differ in that viroids do not possess a protein coat.

Virusoids, while being studied in virology, are subviral particles rather than viruses. Since they depend on helper viruses, they are classified as satellites. In the virological taxonomy they appear as Satellites/Satellite nucleic acids/Subgroup 3: Circular satellite RNA(s).

 

Virophages are small, double stranded DNA viral phages that require the co-infection of another virus. The co-infecting viruses are typically giant viruses. Virophages rely on the viral replication factory of the co-infecting giant virus for their own replication. One of the characteristics of virophages is that they have a parasitic relationship with the co-infecting virus. Their dependence upon the giant virus for replication often results in the deactivation of the giant viruses. The virophage may improve the recovery and survival of the host organism.

Contents
1 Discovery
2 Host Range and Replication
3 Genome
4 Distinguishable Characteristics
5 Taxonomy
6 In popular culture
7 References
Discovery
The first virophage was discovered in a cooling tower in Paris, France. It was discovered with its co-infecting giant virus, Acanthamoeba castellanii mamavirus (ACMV). The virophage was named Sputnik and its replication relied entirely on the co-infection of ACMV and its cytoplasmic replication machinery. Sputnik was also discovered to have an inhibitory effect on ACMV and improved the survival of the host. The most current list of discovered virophages include Sputnik, Sputnik 2, Sputnik 3, Zamilon and Mavirus[1][2]

A majority of these virophages are being discovered by analyzing metagenomic data sets. In metagenomic analysis, DNA data is sequenced and ran through multiple bioinformatic algorithms which, based on what is being analyzed, pull out certain important patterns and characteristics. In these data sets are giant viruses and virophages. They are separated by looking for sequences around 17 to 20 kbp (kilobasepairs) long and have similarities to already sequenced virophages. These virophages can have linear or circular double stranded DNA genomes.[3] Virophages in culture have icosahedral capsid particles that measure around 40 to 80 nanometers long.[4] Virophage particles are so small that electron microscopy must be used to view these particles. Through metagenomic sequence-based analyses, around 57 complete and partial virophage genomes have been identified.[5]

Host Range and Replication
Virophages need to have a co-infecting virus in order for them to replicate. The virophages do not have the necessary enzymes to replicate on their own. Virophages use the giant viral replication machinery to replicate their own genomes and continue their existence. The host range for virophages include giant viruses with double stranded DNA genomes. Virophages use the transcriptional machinery of these giant viruses for their own replication instead of the host's transcriptional machinery. For example, the discovery of the virophage associated with the Samba virus decreased the viruses concentration in the host while the virophage was replicating using the giant virus. The host amoeba also showed a partial recovery from the infection by the Samba virus.[3]

Genome
Virophages have small double stranded DNA genomes that are either circular or linear in shape. The size of these genomes can vary depending on the giant virus it infects. Most virophages have genomes around 17–30 kbp (kilobasepairs).[4][5] Their genome is protected by an icosahedral capsid measuring approximately 40–80 nm in length.[4] In contrast, their co-infecting giant virus counterparts can have genomes as large as 1–2 Mbp (megabasepairs).[3] Some of the largest genomes of virophages are similar to the genome size of an adenovirus.[4]

Genome
Size (kbp)

Particle Size
(diameter, in nm)

Virus: Poliovirus 7 30
Virus: Adenoviridae 26–48 90–100
Virophage: Zamilon Virophage 17 50–60
Virophage: Sputnik Virophage 18 74
Giant Virus: Cafeteria roenbergensis virus 700 75
Giant Virus: Mimivirus 1,181 400–800
Distinguishable Characteristics
Unlike satellite viruses, virophages have a parasitic effect on their co-infecting virus. Virophages have been observed to render a giant virus inactive and thereby improve the condition of the host organism.

Taxonomy
The family Lavidaviridae with the two genera, Sputnikvirus and Mavirus, has been established by the International Committee on Taxonomy of Viruses for classification of virophages.[4]

Family Lavidaviridae
Genus Sputnikvirus
Species Mimivirus-dependent virus Sputnik
Species Mimivirus-dependent virus Zamilon
Genus Mavirus
Species Cafeteriavirus-dependent mavirus
Unassigned genus
Organic Lake virophage
In popular culture
The Radiolab podcast Shrink produced by National Public Radio featured journalist Carl Zimmer discussing giant viruses and virophages.

 

Wirofagi – wirusy niezdolne do samodzielnej replikacji, podgrupa wirusów satelitarnych. Rozwój wirofaga wymaga koinfekcji komórki przez wirofaga i innego wirusa. Po rozpoczęciu namnażania wirusa-ofiary wirofag atakuje go, wykorzystując białka i materiał genetyczny do replikacji własnego wirionu.

Spis treści
1 Poznane wirofagi
2 Odporność
3 Przypisy
4 Bibliografia
Poznane wirofagi
Dotychczas (2013) udało się odkryć i zbadać cztery wirofagi:

Sputnik
Mavirus
OLV (Organic Lake Virophage)
Zamilon
Są to wirusy DNA.

Odporność
Wirofag Zamilon atakuje wirusy Mimivirus, pasożytujące na komórkach ameb Acanthoamoeba polyphaga. W 2016 roku odkryto, że jeden ze szczepów mimiwirusów wykazuje odporność na zakażenie tym wirofagiem. System MIMIVIRE (ang. Mimivirus Virophage Resistance Element) wykorzystuje mechanizm podobny do systemu CRISPR (ang. Clustered Regularly Interspaced Short Palindromic Repeats) występującego u bakterii i archeonów, który sprawdza DNA pod kątem obecności fragmentów z „biblioteki” obcych genów i tnie potencjalnie niebezpieczną nić. Potwierdzeniem tej hipotezy jest fakt, że wyciszenie tego regionu kodu genetycznego mimiwirusa sprawia, że staje się on podatny na atak wirofaga[1][2].

 

A satellite is a subviral agent composed of nucleic acid that depends on the co-infection of a host cell with a helper virus for its replication.

Satellite viruses, which are most commonly associated with plants, but are also found in mammals, arthropods, and bacteria, have the components to make their own protein shell to enclose their genetic material, but rely on a helper virus to replicate. Most viruses have the capability to use host enzymes or their own replication machinery to independently replicate their own viral RNA. Satellite viruses in contrast, are completely dependent on a helper virus for replication. The symbiotic relationship between a satellite and a helper virus to catalyze the replication of a satellite viral genome is also dependent on the host to provide components like replicases[1] to carry out replication.[2] A satellite virus of mamavirus that inhibits the replication of its host has been termed a virophage.[3] However, the usage of this term remains controversial due to the lack of fundamental differences between virophages and classical satellite viruses.[4]

The genomes of satellite viruses range upward from 359 nucleotides in length for satellite tobacco ringspot virus RNA (STobRV).[5]

Satellite viral particles should not be confused with satellite DNA.

Satellite Virus Vs. Virus
Virus Satellite Virus
Replication Able to direct host cell to replicate genome Depends on presence of helper virus for replication of genome
Nucleic acid Contain DNA or RNA or both at different points in life cycle Contain DNA or RNA
Genome Size <10kbp to >2000kbp 0.22–1.5kbp
Structure Contain protein shell or capsid
Packaged genome with a capsid

Envelope - not specific to all viruses

Satellite viruses contain the protein to encode own capsid with aid of helper virus
Satellite RNA's and DNA's do not have capsids, rely on helper virus to enclose their genome

Host Range Can infect all types of organism; animals, plants, fungi, bacteria, archaea Plants (most common), mammals, arthropods, bacteria

Contents
1 History and discovery
2 Classification
3 See also
4 References
5 External links
History and discovery
The tobacco necrosis virus was the virus that lead to the discovery of the first satellite virus in 1962. Scientists discovered that the first satellite had the components to make its own protein shell. A few years later in 1969, scientists discovered another symbiotic relationship with the tobacco ringspot neopvirus (TobRV) and another satellite virus.[6] The emergence of satellite RNA is said to have come from either the genome of the host or its co-infecting agents, and any vectors leading to transmission.[7]

A satellite virus important to human health that demonstrates the need for co-infection to replicate and infect within a host is the virus that causes hepatitis D. Hepatitis D (HDV) was discovered in 1977 by an Mario Rizzetto[8] and is unique from hepatitis A, B, and C because it requires viral particles from hepatitis B to replicate and infect liver cells. Hepatitis B (HBV) provides a surface antigen HBsAg which in return is utilized by HDV to create a super infection resulting in liver failure.[9] Hepatitis delta virus is found all over the globe but most prevalent in Africa, the Middle East and southern Italy.[9]

Classification
Satellite viruses- satellites are classified as sub viral agents in that they require the help for co-infection; therefore, they do not have their own taxonomic classification. There is ongoing talk about proposing new genre for the taxonomic classification of satellites.
Single-stranded RNA satellite viruses
Subgroup 1: Chronic bee paralysis virus associated satellite
Chronic bee-paralysis satellite virus
Subgroup 2: Tobacco necrosis virus satellite
Maize white line mosaic satellite virus
Panicum mosaic satellite virus
Tobacco mosaic satellite virus
Tobacco necrosis satellite virus
Double-stranded DNA satellite viruses
Sputnik virophage
Zamilon virophage
Mavirus virophage
Organic Lake virophage
Satellite nucleic acids
Single-stranded satellite DNAs
Alphasatellites
Tomato leaf curl virus satellite DNA
Betasatellites
Double-stranded satellite RNAs
Saccharomyces cerevisiae M virus satellite
Trichomonas vaginalis T1 virus satellite
Single-stranded satellite RNAs
Subgroup 1: Large satellite RNAs
Arabis mosaic virus large satellite RNA
Bamboo mosaic virus satellite RNA
Chicory yellow mottle virus large satellite RNA
Grapevine Bulgarian latent virus satellite RNA
Grapevine fanleaf virus satellite RNA
Myrobalan latent ringspot virus satellite RNA
Tomato black ring virus satellite RNA
Beet ringspot virus satellite RNA
Subgroup 2: Small linear satellite RNAs
Cucumber mosaic virus satellite RNA
Cymbidium ringspot virus satellite RNA
Pea enation mosaic virus satellite RNA
Groundnut rosette virus satellite RNA
Panicum mosaic virus small satellite RNA
Peanut stunt virus satellite RNA
Turnip crinkle virus satellite RNA
Tomato bushy stunt virus satellite RNA, B10
Tomato bushy stunt virus satellite RNA, B1
Subgroup 3: Circular satellite RNAs or “virusoids”
Arabis mosaic virus small satellite RNA
Cereal yellow dwarf virus-RPV satellite RNA
Chicory yellow mottle virus satellite RNA
Hepatitis D satellite virus RNA
Lucerne transient streak virus satellite RNA
Snake Hepatitis D virus
Solanum nodiflorum mottle virus satellite RNA
Subterranean clover mottle virus satellite RNA
Tobacco ringspot virus satellite RNA
Velvet tobacco mottle virus satellite RNA

 

Wirusy satelitarne – wirusy, których replikacja jest zależna od innych wirusów. Mogą kodować własne białka albo opierać się na innych wirusach zarówno dla enkapsydacji, jak replikacji[1][2][3][4][5].

Pierwszy wirus satelitarny opisano w 1962 r., był on powiązany z wirusem nekrozy tytoniu (TNV, ang. Tobacco necrosis virus)[6]. Niektóre wirusy satelitarne szkodzą wirusom-gospodarzom lub uniemożliwiają ich rozwój; są one nazywane wirofagami.

 

A transposable element (TE, transposon, or jumping gene) is a DNA sequence that can change its position within a genome, sometimes creating or reversing mutations and altering the cell's genetic identity and genome size.[1] Transposition often results in duplication of the same genetic material. Barbara McClintock's discovery of them earned her a Nobel Prize in 1983.[2]

Transposable elements make up a large fraction of the genome and are responsible for much of the mass of DNA in a eukaryotic cell. Although TEs are selfish genetic elements, many are important in genome function and evolution.[3] Transposons are also very useful to researchers as a means to alter DNA inside a living organism.

There are at least two classes of TEs: Class I TEs or retrotransposons generally function via reverse transcription, while Class II TEs or DNA transposons encode the protein transposase, which they require for insertion and excision, and some of these TEs also encode other proteins.[4]

Contents
1 Discovery
2 Classification
2.1 Retrotransposon
2.2 DNA transposons
2.3 Autonomous and non-autonomous
3 Examples
4 In disease
5 Rate of transposition, induction and defense
6 Evolution
7 Applications
8 De novo repeat identification
9 Adaptive TEs
10 See also
11 Notes
11.1 References
12 External links
Discovery
Barbara McClintock discovered the first TEs in maize (Zea mays) at the Cold Spring Harbor Laboratory in New York. McClintock was experimenting with maize plants that had broken chromosomes.[5]

In the winter of 1944–1945, McClintock planted corn kernels that were self-pollinated, meaning that the silk (style) of the flower received pollen from its own anther.[5] These kernels came from a long line of plants that had been self-pollinated, causing broken arms on the end of their ninth chromosomes.[5] As the maize plants began to grow, McClintock noted unusual color patterns on the leaves.[5] For example, one leaf had two albino patches of almost identical size, located side by side on the leaf.[5] McClintock hypothesized that during cell division certain cells lost genetic material, while others gained what they had lost.[6] However, when comparing the chromosomes of the current generation of plants with the parent generation, she found certain parts of the chromosome had switched position.[6] This refuted the popular genetic theory of the time that genes were fixed in their position on a chromosome. McClintock found that genes could not only move, but they could also be turned on or off due to certain environmental conditions or during different stages of cell development.[6]

McClintock also showed that gene mutations could be reversed.[7] She presented her report on her findings in 1951, and published an article on her discoveries in Genetics in November 1953 entitled “Induction of Instability at Selected Loci in Maize”.[8]

Her work was largely dismissed and ignored until the late 1960s–1970s when, after TEs were found in bacteria, it was rediscovered.[9] She was awarded a Nobel Prize in Physiology or Medicine in 1983 for her discovery of TEs, more than thirty years after her initial research.[10]

Approximately 90% of the maize genome is made up of TEs,[11][12] as is 44% of the human genome.[13]

Classification
Transposable elements represent one of several types of mobile genetic elements. TEs are assigned to one of two classes according to their mechanism of transposition, which can be described as either copy and paste (Class I TEs) or cut and paste (Class II TEs).[14]

Retrotransposon
Main article: Retrotransposon
Class I TEs are copied in two stages: first, they are transcribed from DNA to RNA, and the RNA produced is then reverse transcribed to DNA. This copied DNA is then inserted back into the genome at a new position. The reverse transcription step is catalyzed by a reverse transcriptase, which is often encoded by the TE itself. The characteristics of retrotransposons are similar to retroviruses, such as HIV.

Retrotransposons are commonly grouped into three main orders:

Retrotransposons, with long terminal repeats (LTRs), which encode reverse transcriptase, similar to retroviruses
Retroposons, long interspersed nuclear elements (LINEs, LINE-1s, or L1s), which encode reverse transcriptase but lack LTRs, and are transcribed by RNA polymerase II
Short interspersed nuclear elements (SINEs) do not encode reverse transcriptase and are transcribed by RNA polymerase III
(Retroviruses can also be considered TEs. For example, after conversion of retroviral RNA into DNA inside a host cell, the newly produced retroviral DNA is integrated into the genome of the host cell. These integrated DNAs are termed proviruses. The provirus is a specialized form of eukaryotic retrotransposon, which can produce RNA intermediates that may leave the host cell and infect other cells. The transposition cycle of retroviruses has similarities to that of prokaryotic TEs, suggesting a distant relationship between the two.)

DNA transposons

A. Structure of DNA transposons (Mariner type). Two inverted tandem repeats (TIR) flank the transposase gene. Two short tandem site duplications (TSD) are present on both sides of the insert.
B. Mechanism of transposition: Two transposases recognize and bind to TIR sequences, join together and promote DNA double-strand cleavage. The DNA-transposase complex then inserts its DNA cargo at specific DNA motifs elsewhere in the genome, creating short TSDs upon integration.[15]
The cut-and-paste transposition mechanism of class II TEs does not involve an RNA intermediate. The transpositions are catalyzed by several transposase enzymes. Some transposases non-specifically bind to any target site in DNA, whereas others bind to specific target sequences. The transposase makes a staggered cut at the target site producing sticky ends, cuts out the DNA transposon and ligates it into the target site. A DNA polymerase fills in the resulting gaps from the sticky ends and DNA ligase closes the sugar-phosphate backbone. This results in target site duplication and the insertion sites of DNA transposons may be identified by short direct repeats (a staggered cut in the target DNA filled by DNA polymerase) followed by inverted repeats (which are important for the TE excision by transposase).

Cut-and-paste TEs may be duplicated if their transposition takes place during S phase of the cell cycle, when a donor site has already been replicated but a target site has not yet been replicated.[16] Such duplications at the target site can result in gene duplication, which plays an important role in genomic evolution.[17]:284

Not all DNA transposons transpose through the cut-and-paste mechanism. In some cases, a replicative transposition is observed in which a transposon replicates itself to a new target site (e.g. helitron).

Class II TEs comprise less than 2% of the human genome, making the rest Class I.[18]

Autonomous and non-autonomous
Transposition can be classified as either “autonomous” or “non-autonomous” in both Class I and Class II TEs. Autonomous TEs can move by themselves, whereas non-autonomous TEs require the presence of another TE to move. This is often because dependent TEs lack transposase (for Class II) or reverse transcriptase (for Class I).

Activator element (Ac) is an example of an autonomous TE, and dissociation elements (Ds) is an example of a non-autonomous TE. Without Ac, Ds is not able to transpose.

Examples
The first TEs were discovered in maize (Zea mays) by Barbara McClintock in 1948, for which she was later awarded a Nobel Prize. She noticed chromosomal insertions, deletions, and translocations caused by these elements. These changes in the genome could, for example, lead to a change in the color of corn kernels. About 85% of the maize genome consists of TEs.[19] The Ac/Ds system described by McClintock are Class II TEs. Transposition of Ac in tobacco has been demonstrated by B. Baker (Plant Transposable Elements, pp 161–174, 1988, Plenum Publishing Corp., ed. Nelson).
In the pond micro organism, Oxytricha, TEs play such a critical role that when removed, the organism fails to develop.[20]
One family of TEs in the fruit fly Drosophila melanogaster are called P elements. They seem to have first appeared in the species only in the middle of the twentieth century; within the last 50 years, they spread through every population of the species. Gerald M. Rubin and Allan C. Spradling pioneered technology to use artificial P elements to insert genes into Drosophila by injecting the embryo.[21][22][23]
Transposons in bacteria usually carry an additional gene for functions other than transposition, often for antibiotic resistance. In bacteria, transposons can jump from chromosomal DNA to plasmid DNA and back, allowing for the transfer and permanent addition of genes such as those encoding antibiotic resistance (multi-antibiotic resistant bacterial strains can be generated in this way). Bacterial transposons of this type belong to the Tn family. When the transposable elements lack additional genes, they are known as insertion sequences.
The most common transposable element in humans is the Alu sequence. It is approximately 300 bases long and can be found between 300,000 and one million times in the human genome. Alu alone is estimated to make up 15–17% of the human genome.[24]
Mariner-like elements are another prominent class of transposons found in multiple species, including humans. The Mariner transposon was first discovered by Jacobson and Hartl in Drosophila.[25] This Class II transposable element is known for its uncanny ability to be transmitted horizontally in many species.[26][27] There are an estimated 14,000 copies of Mariner in the human genome comprising 2.6 million base pairs.[28] The first mariner-element transposons outside of animals were found in Trichomonas vaginalis.[29] These characteristics of the Mariner transposon inspired the science fiction novel The Mariner Project by Bob Marr.
Mu phage transposition is the best-known example of replicative transposition.
Yeast (Saccharomyces cerevisiae) genomes contain five distinct retrotransposon families: Ty1, Ty2, Ty3, Ty4 and Ty5.[30]
A helitron is a TE found in eukaryotes that is thought to replicate by a rolling-circle mechanism.
In human embryos, two types of transposons combined to form noncoding RNA that catalyzes the development of stem cells. During the early stages of a fetus's growth, the embryo's inner cell mass expands as these stem cells enumerate. The increase of this type of cells is crucial, since stem cells later change form and give rise to all the cells in the body.
In peppered moths, a transposon in a gene called cortex caused the moths' wings to turn completely black. This change in coloration helped moths to blend in with ash and soot-covered areas during the Industrial Revolution.
In disease
TEs are mutagens and their movements are often the causes of genetic disease. They can damage the genome of their host cell in different ways:[31]

a transposon or a retrotransposon that inserts itself into a functional gene will most likely disable that gene;
after a DNA transposon leaves a gene, the resulting gap will probably not be repaired correctly;
multiple copies of the same sequence, such as Alu sequences, can hinder precise chromosomal pairing during mitosis and meiosis, resulting in unequal crossovers, one of the main reasons for chromosome duplication.
Diseases often caused by TEs include hemophilia A and B, severe combined immunodeficiency, porphyria, predisposition to cancer, and Duchenne muscular dystrophy.[32][33] LINE1 (L1) TEs that land on the human Factor VIII have been shown to cause haemophilia[34] and insertion of L1 into the APC gene causes colon cancer, confirming that TEs play an important role in disease development.[35] Transposable element dysregulation can cause neuronal death in Alzheimer's disease and similar tauopathies.[36]

Additionally, many TEs contain promoters which drive transcription of their own transposase. These promoters can cause aberrant expression of linked genes, causing disease or mutant phenotypes.

Rate of transposition, induction and defense
One study estimated the rate of transposition of a particular retrotransposon, the Ty1 element in Saccharomyces cerevisiae. Using several assumptions, the rate of successful transposition event per single Ty1 element came out to be about once every few months to once every few years.[37] Some TEs contain heat-shock like promoters and their rate of transposition increases if the cell is subjected to stress,[38] thus increasing the mutation rate under these conditions, which might be beneficial to the cell.

Cells defend against the proliferation of TEs in a number of ways. These include piRNAs and siRNAs,[39] which silence TEs after they have been transcribed.

If organisms are mostly composed of TEs, one might assume that disease caused by misplaced TEs is very common, but in most cases TEs are silenced through epigenetic mechanisms like DNA methylation, chromatin remodeling and piRNA, such that little to no phenotypic effects nor movements of TEs occur as in some wild-type plant TEs. Certain mutated plants have been found to have defects in methylation-related enzymes (methyl transferase) which cause the transcription of TEs, thus affecting the phenotype.[4][40]

One hypothesis suggests that only approximately 100 LINE1 related sequences are active, despite their sequences making up 17% of the human genome. In human cells, silencing of LINE1 sequences is triggered by an RNA interference (RNAi) mechanism. Surprisingly, the RNAi sequences are derived from the 5' untranslated region (UTR) of the LINE1, a long terminal which repeats itself. Supposedly, the 5' LINE1 UTR that codes for the sense promoter for LINE1 transcription also encodes the antisense promoter for the miRNA that becomes the substrate for siRNA production. Inhibition of the RNAi silencing mechanism in this region showed an increase in LINE1 transcription.[4][41]

Evolution
TEs are found in almost all life forms, and the scientific community is still exploring their evolution and their effect on genome evolution. It is unclear whether TEs originated in the last universal common ancestor, arose independently multiple times, or arose once and then spread to other kingdoms by horizontal gene transfer.[42] While some TEs confer benefits on their hosts, most are regarded as selfish DNA parasites. In this way, they are similar to viruses. Various viruses and TEs also share features in their genome structures and biochemical abilities, leading to speculation that they share a common ancestor.[43]

Because excessive TE activity can damage exons, many organisms have acquired mechanisms to inhibit their activity. Bacteria may undergo high rates of gene deletion as part of a mechanism to remove TEs and viruses from their genomes, while eukaryotic organisms typically use RNA interference to inhibit TE activity. Nevertheless, some TEs generate large families often associated with speciation events. Evolution often deactivates DNA transposons, leaving them as introns (inactive gene sequences). In vertebrate animal cells, nearly all 100,000+ DNA transposons per genome have genes that encode inactive transposase polypeptides.[44] The first synthetic transposon designed for use in vertebrate (including human) cells, the Sleeping Beauty transposon system, is a Tc1/mariner-like transposon. Its dead (“fossil”) versions are spread widely in the salmonid genome and a functional version was engineered by comparing those versions.[45] Human Tc1-like transposons are divided into Hsmar1 and Hsmar2 subfamilies. Although both types are inactive, one copy of Hsmar1 found in the SETMAR gene is under selection as it provides DNA-binding for the histone-modifying protein.[46] Many other human genes are similarly derived from transposons.[47] Hsmar2 has been reconstructed multiple times from the fossil sequences.[48]

Large quantities of TEs within genomes may still present evolutionary advantages, however. Interspersed repeats within genomes are created by transposition events accumulating over evolutionary time. Because interspersed repeats block gene conversion, they protect novel gene sequences from being overwritten by similar gene sequences and thereby facilitate the development of new genes. TEs may also have been co-opted by the vertebrate immune system as a means of producing antibody diversity. The V(D)J recombination system operates by a mechanism similar to that of some TEs.

TEs can contain many types of genes, including those conferring antibiotic resistance and ability to transpose to conjugative plasmids. Some TEs also contain integrons, genetic elements that can capture and express genes from other sources. These contain integrase, which can integrate gene cassettes. There are over 40 antibiotic resistance genes identified on cassettes, as well as virulence genes.

Transposons do not always excise their elements precisely, sometimes removing the adjacent base pairs; this phenomenon is called exon shuffling. Shuffling two unrelated exons can create a novel gene product or, more likely, an intron.[49]

Applications
Main article: Transposons as a genetic tool
The first TE was discovered in maize (Zea mays) and is named dissociator (Ds). Likewise, the first TE to be molecularly isolated was from a plant (snapdragon). Appropriately, TEs have been an especially useful tool in plant molecular biology. Researchers use them as a means of mutagenesis. In this context, a TE jumps into a gene and produces a mutation. The presence of such a TE provides a straightforward means of identifying the mutant allele relative to chemical mutagenesis methods.

Sometimes the insertion of a TE into a gene can disrupt that gene's function in a reversible manner, in a process called insertional mutagenesis; transposase-mediated excision of the DNA transposon restores gene function. This produces plants in which neighboring cells have different genotypes. This feature allows researchers to distinguish between genes that must be present inside of a cell in order to function (cell-autonomous) and genes that produce observable effects in cells other than those where the gene is expressed.

TEs are also a widely used tool for mutagenesis of most experimentally tractable organisms. The Sleeping Beauty transposon system has been used extensively as an insertional tag for identifying cancer genes.[50]

The Tc1/mariner-class of TEs Sleeping Beauty transposon system, awarded Molecule of the Year in 2009,[51] is active in mammalian cells and is being investigated for use in human gene therapy.[52][53][54]

TEs are used for the reconstruction of phylogenies by the means of presence/absence analyses.[55] transposons can act as biological mutagen in bacteria

De novo repeat identification
De novo repeat identification is an initial scan of sequence data that seeks to find the repetitive regions of the genome, and to classify these repeats. Many computer programs exist to perform de novo repeat identification, all operating under the same general principles.[56] As short tandem repeats are generally 1–6 base pairs in length and are often consecutive, their identification is relatively simple.[57] Dispersed repetitive elements, on the other hand, are more challenging to identify, due to the fact that they are longer and have often acquired mutations. However, it is important to identify these repeats as they are often found to be transposable elements (TEs).[56]

De novo identification of transposons involves three steps: 1) find all repeats within the genome, 2) build a consensus of each family of sequences, and 3) classify these repeats. There are three groups of algorithms for the first step. One group is referred to as the k-mer approach, where a k-mer is a sequence of length k. In this approach, the genome is scanned for overrepresented k-mers; that is, k-mers that occur more often than is likely based on probability alone. The length k is determined by the type of transposon being searched for. The k-mer approach also allows mismatches, the number of which is determined by the analyst. Some k-mer approach programs use the k-mer as a base, and extend both ends of each repeated k-mer until there is no more similarity between them, indicating the ends of the repeats.[56] Another group of algorithms employs a method called sequence self-comparison. Sequence self-comparison programs use databases such as AB-BLAST to conduct an initial sequence alignment. As these programs find groups of elements that partially overlap, they are useful for finding highly diverged transposons, or transposons with only a small region copied into other parts of the genome.[58] Another group of algorithms follows the periodicity approach. These algorithms perform a Fourier transformation on the sequence data, identifying periodicities, regions that are repeated periodically, and are able to use peaks in the resultant spectrum to find candidate repetitive elements. This method works best for tandem repeats, but can be used for dispersed repeats as well. However, it is a slow process, making it an unlikely choice for genome scale analysis.[56]

The second step of de novo repeat identification involves building a consensus of each family of sequences. A consensus sequence is a sequence that is created based on the repeats that comprise a TE family. A base pair in a consensus is the one that occurred most often in the sequences being compared to make the consensus. For example, in a family of 50 repeats where 42 have a T base pair in the same position, the consensus sequence would have a T at this position as well, as the base pair is representative of the family as a whole at that particular position, and is most likely the base pair found in the family's ancestor at that position.[56] Once a consensus sequence has been made for each family, it is then possible to move on to further analysis, such as TE classification and genome masking in order to quantify the overall TE content of the genome.

Adaptive TEs
Transposable elements have been recognized as good candidates for stimulating gene adaptation, through their ability to regulate the expression levels of nearby genes.[59] Combined with their “mobility”, transposable elements can be relocated adjacent to their targeted genes, and control the expression levels of the gene, dependent upon the circumstances.

The study conducted in 2008, “High Rate of Recent Transposable Element-Induced Adaptation in Drosophila melanogaster”, used D. melanogaster that had recently migrated from Africa to other parts of the world, as a basis for studying adaptations caused by transposable elements. Although most of the TEs were located on introns, the experiment showed the significant difference on gene expressions between the population in Africa and other parts of the world. The four TEs that caused the selective sweep were more prevalent in D. melanogaster from temperate climates, leading the researchers to conclude that the selective pressures of the climate prompted genetic adaptation.[60] From this experiment, it has been confirmed that adaptive TEs are prevalent in nature, by enabling organisms to adapt gene expression as a result of new selective pressures.

However, not all effects of adaptive TEs are beneficial to the population. In the research conducted in 2009, “A Recent Adaptive Transposable Element Insertion Near Highly Conserved Developmental Loci in Drosophila melanogaster”, a TE, inserted between Jheh 2 and Jheh 3, revealed a downgrade in the expression level of both of the genes. Down regulation of such genes has caused Drosophila to exhibit extended developmental time and reduced egg to adult viability. Although this adaptation was observed in high frequency in all non-African populations, it was not fixed in any of them.[61] This is not hard to believe, since it is logical for a population to favor higher egg to adult viability, therefore trying to purge the trait caused by this specific TE adaptation.

At the same time, there have been several reports showing the advantageous adaptation caused by TEs. In the research done with silkworms, “An Adaptive Transposable Element insertion in the Regulatory Region of the EO Gene in the Domesticated Silkworm”, a TE insertion was observed in the cis-regulatory region of the EO gene, which regulates molting hormone 20E, and enhanced expression was recorded. While populations without the TE insert are often unable to effectively regulate hormone 20E under starvation conditions, those with the insert had a more stable development, which resulted in higher developmental uniformity.[62]

These three experiments all demonstrated different ways in which TE insertions can be advantageous or disadvantageous, through means of regulating the expression level of adjacent genes. The field of adaptive TE research is still under development and more findings can be expected in the future.

 

Transpozon − sekwencja DNA, która może przemieszczać się na inną pozycję w genomie tej samej komórki w wyniku procesu zwanego transpozycją. Transpozycja często powoduje mutacje i może zmieniać ilość DNA w genomie. Transpozony są także nazywane „wędrującymi genami” lub „skaczącymi genami” (ang. jumping genes) oraz “mobilnymi elementami genetycznymi” (ang. mobile genetic elements). Za badania nad transpozonami u kukurydzy, powodującymi zmiany ubarwienia nasion, Barbara McClintock otrzymała Nagrodę Nobla w dziedzinie fizjologii i medycyny w roku 1983.

Rozróżniamy dwie klasy transpozonów:

transpozony klasy I − retrotranspozony: rozprzestrzeniają się, wykorzystując mechanizm transkrypcji na RNA, a następnie przepisania na DNA za pomocą odwrotnej transkryptazy i integracji tak powstałego DNA w inne miejsce genomu;
transpozony klasy II: przemieszczają się w genomie poprzez wycinanie z pierwotnego położenia, następnie „wklejanie się” w nowe miejsce z udziałem transpozazy.
Istnieje hipoteza, że transpozony są dawnymi wirusami, a w szczególności retrowirusami, które utraciły geny odpowiedzialne za zjadliwość. Transpozony nigdy bowiem nie występują poza komórką, jako zdolne do infekcji chorobotwórczych.

Zastosowania
Zdolność transpozonów do aktywnego wbudowywania się w genom wykorzystuje współczesna biologia molekularna, inżynieria genetyczna i biotechnologia. Geny zawarte w transpozonie można bowiem zastąpić innymi, wykorzystując transpozon jako wydajny wektor. Transpozon może też zostać użyty jako sonda molekularna do lokalizowania poszukiwanych sekwencji DNA.

Mechanizmy zabezpieczające genom
Przed przemieszczaniem się transpozonów chronią:

metylacja DNA,
autoregulacja liczby kopii elementów,
preferencje miejsca wbudowywania.
Podział
Transpozony DNA:
Transpozony Procaryota:
sekwencje insercyjne
transpozony złożone
transpozony niezłożone
fagi zdolne do transpozycji
Transpozony Eucaryota
Transpozony RNA (retroelementy):
Elementy LTR:
retrowirusy endogenne
elementy retrowirusopodobne
retrotranspozony
Elementy poly-A (retropozony):
sekwencje LINE
sekwencje SINE

 

Retrotransposons (also called Class I transposable elements or transposons via RNA intermediates) are genetic elements that can amplify themselves in a genome and are ubiquitous components of the DNA of many eukaryotic organisms. These DNA sequences use a “copy-and-paste” mechanism, whereby they are first transcribed into RNA, then converted back into identical DNA sequences using reverse transcription, and these sequences are then inserted into the genome at target sites.

Retrotransposons form one of the two subclasses of transposons, where the others are DNA transposons, which does not involve an RNA intermediate.

Retrotransposons are particularly abundant in plants, where they are often a principal component of nuclear DNA. In maize, 49–78% of the genome is made up of retrotransposons.[1] In wheat, about 90% of the genome consists of repeated sequences and 68% of transposable elements.[2] In mammals, almost half the genome (45% to 48%) is transposons or remnants of transposons. Around 42% of the human genome is made up of retrotransposons, while DNA transposons account for about 2–3%.[3]

Contents
1 Biological activity
2 Types
2.1 LTR retrotransposons
2.1.1 Endogenous retroviruses (ERV)
2.2 Non-LTR retrotransposons
2.2.1 LINEs
2.2.2 SINEs
2.2.2.1 Structure and propagation
2.2.2.2 Types
3 See also
4 References
Biological activity
The retrotransposons' replicative mode of transposition by means of an RNA intermediate rapidly increases the copy numbers of elements and thereby can increase genome size. Like DNA transposable elements (class II transposons), retrotransposons can induce mutations by inserting near or within genes. Furthermore, retrotransposon-induced mutations are relatively stable, because the sequence at the insertion site is retained as they transpose via the replication mechanism.

Retrotransposons copy themselves to RNA and then back to DNA that may integrate back to the genome. The second step of forming DNA may be carried out by a reverse transcriptase, which the retrotransposon encodes.[4] Transposition and survival of retrotransposons within the host genome are possibly regulated both by retrotransposon- and host-encoded factors, to avoid deleterious effects on host and retrotransposon as well. The understanding of how retrotransposons and their hosts' genomes have co-evolved mechanisms to regulate transposition, insertion specificities, and mutational outcomes in order to optimize each other's survival is still in its infancy.

Because of accumulated mutations, most retrotransposons are no longer able to retrotranspose.

Types
Retrotransposons, also known as class I transposable elements, consist of two subclasses, the long terminal repeat (LTR-retrotransposons) and the non-LTR retrotransposons. Classification into these subclasses is based on the phylogeny of the reverse transcriptase,[5] which goes in line with structural differences, such as presence/absence of long terminal repeats as well as number and types of open reading frames, encoding domains and target site duplication lengths.

LTR retrotransposons
Main article: LTR retrotransposon
LTR retrotransposons have direct LTRs that range from ~100 bp to over 5 kb in size. LTR retrotransposons are further sub-classified into the Ty1-copia-like (Pseudoviridae), Ty3-gypsy-like (Metaviridae), and BEL-Pao-like groups based on both their degree of sequence similarity and the order of encoded gene products. Ty1-copia and Ty3-gypsy groups of retrotransposons are commonly found in high copy number (up to a few million copies per haploid nucleus) in animals, fungi, protista, and plants genomes. BEL-Pao like elements have so far only been found in animals.[6][7]

Although retroviruses are often classified separately, they share many features with LTR retrotransposons. A major difference with Ty1-copia and Ty3-gypsy retrotransposons is that retroviruses have an envelope protein (ENV). A retrovirus can be transformed into an LTR retrotransposon through inactivation or deletion of the domains that enable extracellular mobility. If such a retrovirus infects and subsequently inserts itself in the genome in germ line cells, it may become transmitted vertically and become an Endogenous Retrovirus (ERV).[7] Endogenous retroviruses make up about 8% of the human genome and approximately 10% of the mouse genome.[8]

In plant genomes, LTR retrotransposons are the major repetitive sequence class, e.g. able to constitute more than 75% of the maize genome.[9]

Endogenous retroviruses (ERV)
Main article: Endogenous retrovirus
Endogenous retroviruses are an important type of LTR retrotransposon in mammals, including in humans where the Human ERVs make up 8% of the genome.

Genetic structure of murine LINE1 and SINEs. Bottom: proposed structure of L1 RNA-protein (RNP) complexes. ORF1 proteins form trimers, exhibiting RNA binding and nucleic acid chaperone activity.[10]
Non-LTR retrotransposons
Non-LTR retrotransposons consist of two sub-types, long interspersed elements (LINEs) and short interspersed elements (SINEs). They can also be found in high copy numbers, as shown in the plant species.[11] Non-long terminal repeat (LTR) retroposons are widespread in eukaryotic genomes. LINEs possess two ORFs, which encode all the functions needed for retrotransposition. These functions include reverse transcriptase and endonuclease activities, in addition to a nucleic acid-binding property needed to form a ribonucleoprotein particle.[12] SINEs, on the other hand, co-opt the LINE machinery and function as nonautonomous retroelements. While historically viewed as “junk DNA”, recent research suggests that, in some rare cases, both LINEs and SINEs were incorporated into novel genes so as to evolve new functionality.[13][14]

LINEs
Main article: Long interspersed nuclear element
Long INterspersed Elements[15] (LINE) are a group of genetic elements that are found in large numbers in eukaryotic genomes, comprising 17% of the human genome (99.9% of which is no longer capable of retrotransposition, and therefore considered “dead” or inactive).[16] Among the LINE, there are several subgroups, such as L1, L2 and L3. Human coding L1 begin with an untranslated region (UTR) that includes an RNA polymerase II promoter, two non-overlapping open reading frames (ORF1 and ORF2), and ends with another UTR.[16] Recently, a new open reading frame in the 5' end of the LINE elements has been identified in the reverse strand. It is shown to be transcribed and endogenous proteins are observed. The name ORF0 is coined due to its position with respect to ORF1 and ORF2.[17] ORF1 encodes an RNA binding protein and ORF2 encodes a protein having an endonuclease (e.g. RNase H) as well as a reverse transcriptase. The reverse transcriptase has a higher specificity for the LINE RNA than other RNA, and makes a DNA copy of the RNA that can be integrated into the genome at a new site.[18] The endonuclease encoded by non-LTR retroposons may be AP (Apurinic/Pyrimidinic) type or REL (Restriction Endonuclease Like) type. Elements in the R2 group have REL type endonuclease, which shows site specificity in insertion.[19]

The 5' UTR contains the promoter sequence, while the 3' UTR contains a polyadenylation signal (AATAAA) and a poly-A tail.[20] Because LINEs (and other class I transposons, e.g. LTR retrotransposons and SINEs) move by copying themselves (instead of moving by a cut and paste like mechanism, as class II transposons do), they enlarge the genome. The human genome, for example, contains about 500,000 LINEs, which is roughly 17% of the genome.[21] Of these, approximately 7,000 are full-length, a small subset of which are capable of retrotransposition.[22][23]

Specific LINE-1 retroposons in the human genome are transcribed and the associated LINE-1 RNAs are tightly bound to nucleosomes and essential in the establishment of local chromatin environment.[24]

SINEs
Main article: Short interspersed nuclear element
Short INterspersed Elements[15] (SINEs) are a group of non-LTR (long terminal repeat) and non-autonomous retrotransposons.

SINEs are the only TEs that are non-autonomous by nature, meaning that they did not evolve from autonomous elements. They are small (80- 500 bases[25])) and rely in trans on functional LINEs for their replication, but their evolutionary origin is very distinct. SINEs can be found in very diverse eukaryotes, but they have only accumulated to impressive amount in mammals, where they represent between 5 and 15% of the genome with millions of copies.

Structure and propagation
SINEs typically possess a “head” with an RNA pol III promoter that enables autonomous transcription, and a body of various composition[26]. SINEs are postulated to originate from the accidental retrotransposition of various RNA pol III transcripts, and have appeared separately numerous times in evolution history. The type of RNA pol III promoter defines the different superfamilies and reveal their origin: tRNA, 5S ribosomal RNA or signal recognition particle 7SL RNA.

SINEs do not encode a functional reverse transcriptase protein and rely on other mobile elements for the transposition, especially LINEs[27]. SINE RNAs form a complex with LINE ORF2 proteins and are inserted into the genome by target primed reverse transcription, creating short TSDs upon insertion. Some SINE families are thought to rely on specific LINEs for their replication, while others seem to be more generalist.

Alu and B1 elements, with their 1.1 million and 650,000 copies in the human and mouse genomes, respectively, harbor a 7SL promoter. The 350,000 copies of B2 SINEs in the mouse are on the other hand tRNA-related.

Types
Alu and B1 elements, with their 1.1 million and 650,000 copies in the human and mouse genomes, respectively, harbor a 7SL promoter.

The 350,000 copies of B2 SINEs in the mouse are on the other hand tRNA- related.

The most common SINE in primates is Alu. Alu elements are approximately 350 base pairs long, do not contain any coding sequences, and can be recognized by the restriction enzyme AluI (hence the name). The distribution of these elements has been implicated in some genetic diseases and cancers.

Hominid genomes contain also original elements termed SVA. They are composite transposons formed by the fusion of a SINE-R and an Alu, separated by a variable number of tandems repeats. Less than 3kb in length and apparently mobilized using LINE1 machinery, they are around 2500–3000 copies in human or gorilla genomes, and less than 1000 in orangutan. SVA are one of the youngest transposable element in great apes genome and among the most active and polymorphic in the human population.

See also
Transposon
Endogenous retrovirus
Paleogenetics
Paleovirology
Insertion sequences
Copy-number variation
Genomic organization
Interspersed repeat
Retrotransposon markers, a powerful method of reconstructing phylogenies.
RetrOryza

Retrotranspozon – typ transpozonu (transpozon RNA), stanowiący znaczną część genomów organizmów eukariotycznych. Wszystkie retrotranspozony występują w postaci cząsteczki RNA. Retrotranspozony zawierają geny kodujące enzymy niezbędne do przemieszczania się w procesie transpozycji – po wniknięciu do komórki gospodarza (lub po transkrypcji retrotranspozonu zintegrowanego z genomem gospodarza) następuje synteza pierwszej nici DNA przez enzym zwany odwrotną transkryptazą[1]. W ten sposób powstaje pozachromosomowa, dwuniciowa cząsteczka zbudowana z jednej nici RNA i jednej nici DNA. Następnie matrycowa nić RNA jest wytrawiana (przez enzym RNA-zę), a na jej miejsce syntetyzowana jest druga (komplementarna do pierwszej) nić DNA. Taki dwuniciowy DNA zostaje za pomocą enzymu integrazy wstawiony do genomu gospodarza[2].

Istnieją dwa typy retrotranspozonów[1]:

zawierające na obu końcach długie powtórzone sekwencje nukleotydów – LTR (z ang. Long Terminal Repeats);
nieposiadające sekwencji LTR – non-LTR.
Przykładem retrotranspozonów zawierających sekwencje LTR należą: retrowirusy (u zwierząt)[2], Ty1-copia oraz Ty3-gypsy[3]. Do retrotranspozonów niezawierających sekwencji LTR zalicza się elementy LINE oraz SINE[1].

Spis treści
1 Budowa retrotranspozonów
2 Retrotranspozony LTR
3 Retrotranspozony non-LTR
4 Przypisy
Budowa retrotranspozonów
Retrotranspozony zbudowane są z trzech ważnych genów: gag, pol oraz int. Syntetyzowane są jako poliproteina a następnie cięte przez specyficzną proteazę kodowaną przez gen pol. Gen gag koduje białka biorące udział w dojrzewaniu i pakowaniu retrotranspozonów w celu ich integracji do genomu, gen pol – odwrotną transkryptazę i RNazę H, a gen int – integrazę[3].

Retrotranspozony LTR
Retrotranspozony Ty1-copa oraz Ty3-gypsy wykazują podobną budowę oraz funkcję. Różnice obserwuje się w dwóch genach: int oraz pol[3].

Retrotranspozony non-LTR
Elementy LINE (z ang. Long Interspersed Nuclear Elements) – retrotranspozony zawierające gen pol oraz gag co umożliwia ich trankrypcję i integrację do genomu. Nie stwierdzono u nich genu int[3]. Stanowią około 20% ludzkiego genomu (ich liczbę szacuje się na 500 – 900 tys., jednak tylko około 100 uważa się za nadal aktywne). Elementy LINE mają zwykle ponad 5000 par zasad długości. Czasem powielają też inne sekwencje, np. sekwencje Alu. Wykorzystuje się je w badaniach tzw. genetycznych odcisków palców (zobacz też RFLP).
SINE (z ang. Short Interspersed Nuclear Elements) to krótkie sekwencje stanowiące ok. 10% ludzkiego genomu, które nie kodują funkcjonalnych białek i do przemieszczania się wykorzystują inne retrotranspozony (np. LINE). Najbardziej rozpowszechnione SINE u naczelnych to sekwencje Alu.
Retrotranspozycja może być przyczyną chorób genetycznych, jeśli integracja spowoduje uszkodzenie genu. Odwrotna transkryptaza elementów LINE prawdopodobnie odgrywa rolę w powstawaniu niektórych nowotworów, ale także w normalnym rozwoju embrionalnym u myszy. Sekwencje pochodzące z retrotranspozonów wykorzystywane są jako sekwencje regulatorowe niektórych genów.

 

An endogenous viral element (EVE) is a DNA sequence derived from a virus, and present within the germline of a non-viral organism. EVEs may be entire viral genomes (proviruses), or fragments of viral genomes. They arise when a viral DNA sequence becomes integrated into the genome of a germ cell that goes on to produce a viable organism. The newly established EVE can be inherited from one generation to the next as an allele in the host species, and may even reach fixation.

Endogenous retroviruses and other EVEs that occur as proviruses can potentially remain capable of producing infectious virus in their endogenous state. Replication of such 'active' endogenous viruses can lead to the proliferation of viral insertions in the germline. For most non-retroviral viruses, germline integration appears to be a rare, anomalous event, and the resulting EVEs are often only fragments of the parent virus genome. Such fragments are usually not capable of producing infectious virus, but may express protein or RNA and even cell surface receptors.

Contents
1 Diversity and distribution
2 Use in paleovirology
3 Co-option and exaptation by host species
4 See also
5 References
Diversity and distribution
EVEs have been identified in animals, plants and fungi.[1][2][3][4] In vertebrates EVEs derived from retroviruses (endogenous retroviruses) are relatively common. Because retroviruses integrate into the nuclear genome of the host cell as an inherent part of their replication cycle, they are predisposed to enter the host germline. In addition, EVEs related to parvoviruses, filoviruses, bornaviruses and circoviruses have been identified in vertebrate genomes. In plant genomes, EVEs derived from pararetroviruses are relatively common. EVEs derived from other, non-retrotranscribing virus families, such as Geminiviridae, have also been identified in plants.

Use in paleovirology
EVEs are a rare source of retrospective information about ancient viruses. Many are derived from germline integration events that occurred millions of years ago, and can be viewed as viral fossils. Such ancient EVEs are an important component of paleovirological studies that address the long-term evolution of viruses. Identification of orthologous EVE insertions enables the calibration of long-term evolutionary timelines for viruses, based on the estimated time since divergence of the ortholog-containing host species groups. This approach has provided minimum ages ranging from 30–93 million years for the Parvoviridae, Filoviridae, Bornaviridae and Circoviridae families of viruses,[3] and 12 million years for the Lentivirus genus of the Retroviridae family. EVEs also facilitate the use of molecular clock-based approaches to obtain calibrations of viral evolution in deep time.[5][6]

Co-option and exaptation by host species
EVEs can sometimes provide a selective advantage to the individuals in which they are inserted. For example, some protect against infection with related viruses.[7] [8] In some mammal groups, including higher primates, retroviral envelope proteins have been exapted to produce a protein that is expressed in the placental syncytiotrophoblast, and is involved in fusion of the cytotrophoblast cells to form the syncytial layer of the placenta. In humans this protein is called syncytin, and is encoded by an endogenous retrovirus called (ERVWE1) on chromosome seven. Remarkably, the capture of syncytin or syncytin-like genes has occurred independently, from different groups of endogenous retroviruses, in diverse mammalian lineages. Distinct, syncytin-like genes have been identified in primates, rodents, lagomorphs, carnivores, and ungulates, with integration dates ranging from 10 to 85 million years ago.[9]

See also
Ancient DNA
Avian sarcoma leukosis virus (ASLV)
Endogenous retrovirus
ERV3
HERV-FRD
Jaagsiekte sheep retrovirus (JSRV)
Koala retrovirus (KoRV)
Mouse mammary tumor virus (MMTV)
Murine leukemia virus (MLV), and xenotropic murine leukemia virus-related virus (XMRV)
Paleovirology
Polydnavirus
Viral eukaryogenesis

Viral eukaryogenesis is the hypothesis that the cell nucleus of eukaryotic life forms evolved from a large DNA virus in a form of endosymbiosis within a methanogenic archaeon. The virus later evolved into the eukaryotic nucleus by acquiring genes from the host genome and eventually usurping its role. The hypothesis was proposed by Philip Bell in 2001[1] and gained support[vague] as large, complex DNA viruses (such as Mimivirus) capable of protein biosynthesis were discovered. Recent supporting evidence includes the discovery that, upon the infection of a bacterial cell, the giant bacteriophage 201Phi2–1 (of genus Phikzvirus) assembles a nucleus-like structure that segregates proteins according to function [2]. This nucleus-like structure and its key properties have been found conserved in the related phages[3].

The viral eukaryogenesis hypothesis has inflamed the longstanding debate over whether viruses are living organisms. Many biologists do not consider viruses to be alive, but the hypothesis posits that viruses are the originators of the DNA genetic mechanism shared by all eukaryotes alive today (and possibly that of prokaryotes as well).[4]

Critics of the theory point out that the similarities between DNA viruses and nuclei can be taken as evidence either of viral eukaryogensis or of its converse, nuclear viriogenesis: that complex eukaryotic DNA viruses could have originated from infectious nuclei.[4]

Contents
1 Hypothesis
2 Implications
3 See also
4 References
5 Further reading
Hypothesis
The viral eukaryogenesis hypothesis posits that eukaryotes are composed of three ancestral elements: a viral component that became the modern nucleus; a prokaryotic cell (an archaeon according to eocyte hypothesis) which donated the cytoplasm and cell membrane of modern cells; and another prokaryotic (bacterial) cell that, by endocytosis, became the modern mitochondrion or chloroplast.

In 2006, researchers suggested that the transition from RNA to DNA genomes first occurred in the viral world.[5] A DNA-based virus may have provided storage for an ancient host that had previously used RNA to store its genetic information (such host is called ribocell or ribocyte).[4] Viruses may initially have adopted DNA as a way to resist RNA-degrading enzymes in the host cells. Hence, the contribution from such a new component may have been as significant as the contribution from chloroplasts or mitochondria. Following this hypothesis, archaea, bacteria, and eukaryotes each obtained their DNA informational system from a different virus.[5] In the original paper it was also an RNA cell at the origin of eukaryotes, but eventually more complex, featuring RNA processing. Although this is in contrast to nowadays more probable eocyte hypothesis, viruses seem to have contributed to the origin of all three domains of life ('out of virus hypothesis'). It has also been suggested that telomerase and telomeres, key aspects of eukaryotic cell replication, have viral origins. Further, the viral origins of the modern eukaryotic nucleus may have relied on multiple infections of archaeal cells carrying bacterial mitochondrial precursors with lysogenic viruses.[6] The viral eukaryogenesis hypothesis depicts a model of eukaryotic evolution in which a virus, similar to a modern pox virus, evolved into a nucleus via gene acquisition from existing bacterial and archaeal species [7]. The lysogenic virus then became the information storage center for the cell, while the cell retained its capacities for gene translation and general function despite the viral genome's entry. Similarly, the bacterial species involved in this eukaryogenesis retained its capacity to produce energy in the form of ATP while also passing much of its genetic information into this new virus-nucleus organelle. It is hypothesized that the modern cell cycle, whereby mitosis, meiosis, and sex occur in all eukaryotes, evolved because of the balances struck by viruses, which characteristically follow a pattern of tradeoff between infecting as many hosts as possible and killing an individual host through viral proliferation. Hypothetically, viral replication cycles may mirror those of plasmids and viral lysogens. However, this theory is controversial, and additional experimentation involving archaeal viruses is necessary, as they are probably the most evolutionarily similar to modern eukaryotic nuclei.[8][9]

The viral eukaryogenesis hypothesis points to the cell cycle of eukaryotes, particularly sex and meiosis, as evidence.[8] Little is known about the origins of DNA or reproduction in prokaryotic or eukaryotic cells. It is thus possible that viruses were involved in the creation of Earth's first cells.[10] Like viruses,[which?] a eukaryotic nucleus contains linear chromosomes with specialized end sequences (in contrast to bacterial genomes, which have a circular topology); it uses mRNA capping, and separates transcription from translation. Eukaryotic nuclei are also capable of cytoplasmic replication. Some large viruses have their own DNA-directed RNA polymerase.[4] Transfers of “infectious” nuclei have been documented in many parasitic red algae.[11] Another supporting evidence is that the m7G capping apparatus (involved in uncoupling of transcription from translation) is present in both Eukarya and Mimiviridae but not in Lokiarchaeota that are considered the nearest archaeal relatives of Eukarya according to the Eocyte hypothesis (also supported by the phylogenetic analysis of the m7G capping pathway).[9]

Implications
A number of precepts in the theory are possible. For instance, a helical virus with a bilipid envelope bears a distinct resemblance to a highly simplified cellular nucleus (i.e., a DNA chromosome encapsulated within a lipid membrane). In theory, a large DNA virus could take control of a bacterial or archaeal cell. Instead of replicating and destroying the host cell, it would remain within the cell, thus overcoming the tradeoff dilemma typically faced by viruses. With the virus in control of the host cell's molecular machinery, it would effectively become a functional nucleus. Through the processes of mitosis and cytokinesis, the virus would thus recruit the entire cell as a symbiont—a new way to survive and proliferate.

 

Eukariogeneza – zaproponowana przez Philipa Bella w 2001 roku hipoteza mówiąca o tym, że jądra komórkowe eukariotycznych form życia ewoluowały z wielkiego DNA wirusów w procesie endosymbiozy z komórkami archeonów stając się formą symbiogenezy.

 

Endogenous retroviruses (ERVs) are endogenous viral elements in the genome that closely resemble and can be derived from retroviruses. They are abundant in the genomes of jawed vertebrates, and they comprise up to 5–8% of the human genome (lower estimates of ~1%).[1][2] ERVs are a subclass of a type of gene called a transposon, which can be packaged and moved within the genome to serve a vital role in gene expression and in regulation.[3][4] They are distinguished as retrotransposons, which are Class I elements.[5] Researchers have suggested that retroviruses evolved from a type of transposable gene called a retrotransposon, which includes ERVs; these genes can mutate and instead of moving to another location in the genome they can become exogenous or pathogenic. This means that not all ERVs may have originated as an insertion by a retrovirus but that some may have been the source for the genetic information in the retroviruses they resemble.[6] When integration of viral DNA occurs in the germ-line, it can give rise to an ERV, which can later become fixed in the gene pool of the host population.[1][7]

Contents
1 Formation
2 Role in genome evolution
3 Role in disease
4 Role in medicine
4.1 Porcine endogenous retrovirus
5 Human endogenous retroviruses
6 Techniques for characterizing ERVs
6.1 Whole genome sequencing
6.2 Chromatin Immunoprecipitation with sequencing (ChIP-seq)
7 Applications
7.1 Constructing phylogenies
7.2 Designating the age of provirus and the time points of species separation events
8 Further research
8.1 Epigenetic variability
8.2 Immunological problems of xenotransplantation
8.3 Risk factors of HERVs in gene therapy
8.4 HERV gene expression
9 See also
10 References
11 Further reading
12 External links
Formation
The replication cycle of a retrovirus entails the insertion (“integration”) of a DNA copy of the viral genome into the nuclear genome of the host cell. Most retroviruses infect somatic cells, but occasional infection of germline cells (cells that produce eggs and sperm) can also occur. Rarely, retroviral integration may occur in a germline cell that goes on to develop into a viable organism. This organism will carry the inserted retroviral genome as an integral part of its own genome—an “endogenous” retrovirus (ERV) that may be inherited by its offspring as a novel allele. Many ERVs have persisted in the genome of their hosts for millions of years. However, most of these have acquired inactivating mutations during host DNA replication and are no longer capable of producing the virus. ERVs can also be partially excised from the genome by a process known as recombinational deletion, in which recombination between the identical sequences that flank newly integrated retroviruses results in deletion of the internal, protein-coding regions of the viral genome.

The general retrovirus genome consists of three genes vital for the invasion, replication, escape, and spreading of its viral genome. These three genes are gag (encodes for structural proteins for the viral core), pol (encodes for reverse transcriptase, integrase, and protease), and env (encodes for coat proteins for the virus's exterior). These viral proteins are encoded as polyproteins. In order to carry out their life cycle, the retrovirus relies heavily on the host cell's machinery. Protease degrades peptide bonds of the viral polyproteins, making the separate proteins functional. Reverse transcriptase functions to synthesize viral DNA from the viral RNA in the host cell's cytoplasm before it enters the nucleus. Integrase guides the integration of viral DNA into the host genome.[7][8]

Role in genome evolution
Integration of viral DNA into host genome.png
Endogenous retroviruses can play an active role in shaping genomes. Most studies in this area have focused on the genomes of humans and higher primates, but other vertebrates, such as mice and sheep, have also been studied in depth.[9][10][11][12] The long terminal repeat (LTR) sequences that flank ERV genomes frequently act as alternate promoters and enhancers, often contributing to the transcriptome by producing tissue-specific variants. In addition, the retroviral proteins themselves have been co-opted to serve novel host functions, particularly in reproduction and development. Recombination between homologous retroviral sequences has also contributed to gene shuffling and the generation of genetic variation. Furthermore, in the instance of potentially antagonistic effects of retroviral sequences, repressor genes have co-evolved to combat them.

Solo LTRs and LTRs associated with complete retroviral sequences have been shown to act as transcriptional elements on host genes. Their range of action is mainly by insertion into the 5' UTRs of protein coding genes; however, they have been known to act upon genes up to 70–100 kb away.[9][13][14][15] The majority of these elements are inserted in the sense direction to their corresponding genes, but there has been evidence of LTRs acting in the antisense direction and as a bidirectional promoter for neighboring genes.[16][17] In a few cases, the LTR functions as the major promoter for the gene. For example, in humans AMY1C has a complete ERV sequence in its promoter region; the associated LTR confers salivary specific expression of the digestive enzyme amylase.[18] Also, the primary promoter for bile acid-CoA:amino acid N-acyltransferase (BAAT), which codes for an enzyme that is integral in bile metabolism, is of LTR origin.[14][19]

The insertion of a solo ERV-9 LTR may have produced a functional open reading frame (ORF), causing the rebirth of the human immunity related GTPase gene (IRGM).[20] ERV insertions have also been shown to generate alternative splice sites either by direct integration into the gene, as with the human leptin hormone receptor, or driven by the expression of an upstream LTR, as with the phospholipase A-2 like protein.[21]

Most of the time, however, the LTR functions as one of many alternate promoters, often conferring tissue-specific expression related to reproduction and development. In fact, 64% of known LTR-promoted transcription variants are expressed in reproductive tissues.[22] For example, the gene CYP19 codes for aromatase P450, an important enzyme for estrogen synthesis, that is normally expressed in the brain and reproductive organs of most mammals.[14] However, in primates, an LTR-promoted transcriptional variant confers expression to the placenta and is responsible for controlling estrogen levels during pregnancy.[14] Furthermore, the neuronal apoptosis inhibitory protein (NAIP), normally widespread, has an LTR of the HERV-P family acting as a promoter that confers expression to the testis and prostate.[23] Other proteins, such as nitric oxide synthase 3 (NOS3), interleukin-2 receptor B (IL2RB), and another mediator of estrogen synthesis, HSD17B1, are also alternatively regulated by LTRs that confer placental expression, but their specific functions are not yet known.[19][24] The high degree of reproductive expression is thought to be an after effect of the method by which they were endogenized; however, this also may be due to a lack of DNA methylation in germ-line tissues.[19]

The best-characterized instance of placental protein expression comes not from an alternatively promoted host gene but from a complete co-option of a retroviral protein. Retroviral fusogenic env proteins, which play a role in the entry of the virion into the host cell, have had an important impact on the development of the mammalian placenta. In mammals, intact env proteins called syncytins are responsible for the formation and function of syncytiotrophoblasts.[11] These multinucleated cells are mainly responsible for maintaining nutrient exchange and separating the fetus from the mother's immune system.[11] It has been suggested that the selection and fixation of these proteins for this function have played a critical role in the evolution of viviparity.[25]

In addition, the insertion of ERVs and their respective LTRs have the potential to induce chromosomal rearrangement due to recombination between viral sequences at inter-chromosomal loci. These rearrangements have been shown to induce gene duplications and deletions that largely contribute to genome plasticity and dramatically change the dynamic of gene function.[26] Furthermore, retroelements in general are largely prevalent in rapidly evolving, mammal-specific gene families whose function is largely related to the response to stress and external stimuli.[14] In particular, both human class I and class II MHC genes have a high density of HERV elements as compared to other multi-locus-gene families.[21] It has been shown that HERVs have contributed to the formation of extensively duplicated duplicon blocks that make up the HLA class 1 family of genes.[27] More specifically, HERVs primarily occupy regions within and between the break points between these blocks, suggesting that considerable duplication and deletions events, typically associated with unequal crossover, facilitated their formation.[28] The generation of these blocks, inherited as immunohaplotypes, act as a protective polymorphism against a wide range of antigens that may have imbued humans with an advantage over other primates.[27]

Finally, the insertion of ERVs or ERV elements into genic regions of host DNA, or overexpression of their transcriptional variants, has a much higher potential to produce deleterious effects than positive ones. Their appearance into the genome has created a host-parasite co-evolutionary dynamic that proliferated the duplication and expansion of repressor genes. The most clear-cut example of this involves the rapid duplication and proliferation of tandem zinc-finger genes in mammal genomes. Zinc-finger genes, particularly those that include a KRAB domain, exist in high copy number in vertebrate genomes, and their range of functions are limited to transcriptional roles.[29] It has been shown in mammals, however, that the diversification of these genes was due to multiple duplication and fixation events in response to new retroviral sequences or their endogenous copies to repress their transcription.[15] The characteristic of placentas being very evolutionary distinct organs between different species has been suggested to result from the co-option of ERV enhancers. Regulatory mutations, instead of mutations in genes that encode for hormones and growth factors, support the known evolution of placental morphology, especially since the majority of hormone and growth factor genes are expressed in response to pregnancy, not during placental development. Researchers studied the regulatory landscape of placental development between the rat and mouse, two closely related species. This was done by mapping all regulatory elements of the rat trophoblast stem cells (TSCs) and comparing them to their orthologs in mouse TSCs. TSCs were observed because they reflect the initial cells that develop in the fetal placenta. Regardless of their tangible similarities, enhancer and repressed regions were mostly species-specific. However, most promoter sequences were conserved between mouse and rat. In conclusion to their study, researchers proposed that ERVs influenced species-specific placental evolution through mediation of placental growth, immunosuppression, and cell fusion.[30]

Another example of ERV exploiting cellular mechanisms is p53, a tumor suppressor gene (TSG). DNA damage and cellular stress induces the p53 pathway, which results in cell apoptosis. Using chromatin immunoprecipitation with sequencing, thirty-percent of all p53-binding sites were located within copies of a few primate-specific ERV families. A study suggested that this benefits retroviruses because p53's mechanism provides a rapid induction of transcription, which leads to the exit of viral RNA from the host cell.[5]

Role in disease
The majority of ERVs that occur in vertebrate genomes are ancient, inactivated by mutation, and have reached genetic fixation in their host species. For these reasons, they are extremely unlikely to have negative effects on their hosts except under unusual circumstances. Nevertheless, it is clear from studies in birds and non-human mammal species including mice, cats and koalas, that younger (i.e., more recently integrated) ERVs can be associated with disease. The number of active ERVs in the genome of mammals is negatively related to their body size suggesting a contribution to the Peto's paradox through cancer pathogenesis.[31] This has led researchers to propose a role for ERVs in several forms of human cancer and autoimmune disease, although conclusive evidence is lacking.[32][33][34][35]

In humans, ERVs have been proposed to be involved in multiple sclerosis (MS). A specific association between MS and the ERVWE1, or “syncytin”, gene, which is derived from an ERV insertion, has been reported, along with the presence of an “MS-associated retrovirus” (MSRV), in patients with the disease.[36][37] Human ERVs (HERVs) have also been implicated in ALS[38] and addiction.[39][40][41]

In 2004 it was reported that antibodies to HERVs were found in greater frequency in the sera of people with schizophrenia. Additionally, the cerebrospinal fluid of people with recent onset schizophrenia contained levels of a retroviral marker, reverse transcriptase, four times higher than control subjects.[42] Researchers continue to look at a possible link between HERVs and schizophrenia, with the additional possibility of a triggering infection inducing schizophrenia.[43]

ERVs have been found to be associated to disease not only through disease-causing relations, but also through immunity. The frequency of ERVs in long terminal repeats (LTRs) likely correlates to viral adaptations to take advantage of immunity signaling pathways that promote viral transcription and replication. A study done in 2016 investigated the benefit of ancient viral DNA integrated into a host through gene regulation networks induced by interferons, a branch of innate immunity.[44] These cytokines are first to respond to viral infection and are also important in immunosurveillance for malignant cells.[45] ERVs are predicted to act as cis-regulatory elements, but much of the adaptive consequences of this for certain physiological functions is still unknown. There is data that supports the general role of ERVs in the regulation of human interferon response, specifically to interferon-gamma (IFNG). For example, interferon-stimulated genes were found to be greatly enriched with ERVs bound by signal transducer and activator of transcription (STAT1) and/or Interferon regulatory factor (IRF1) in CD14+ macrophages.[1]

Another idea proposed was that ERVs from the same family played a role in recruiting multiple genes into the same network of regulation. It was found that MER41 elements provided addition redundant regulatory enhancement to the genes located near STAT1 binding sites.[1]

Role in medicine
Porcine endogenous retrovirus
See also: Xenotransplantation § Porcine endogenous retroviruses
For humans, porcine endogenous retroviruses (PERVs) pose a concern when using porcine tissues and organs in xenotransplantion, the transplanting of living cells, tissues, and organs from an organism of one species to an organism of different species. Although pigs are generally the most suitable donors to treat human organ diseases due practical, financial, safety, and ethical reasons,[44] PERVs previously could not be removed from pigs due to its viral nature of integrating into the host genome and being passed into offspring. Until the year 2017 when Dr. George Church's lab removed all 62 retroviruses from the pigs genome.[46] The consequences of cross-species transmission remains unexplored and has very dangerous potential.[47]

Researchers indicated that infection of human tissues by PERVs is very possible, especially in immunosuppressed individuals. An immunosuppressed condition could potentially permit a more rapid and tenacious replication of viral DNA, and would later on have less difficulty adapting to human-to-human transmission. Although known infectious pathogens present in the donor organ/tissue can be eliminated by breeding pathogen-free herds, unknown retroviruses can be present in the donor. These retroviruses are often latent and asymptomatic in the donor, but can become active in the recipient. Some examples of endogenous viruses that can infect and multiply in human cells are from baboons (BaEV), cats (RD114), and mice.[44]

There are three different classes of PERVs, PERV-A, PERV-B, and PERV-C. PERV-A and PERV-B are polytropic and can infect human cells in vitro, while PERV-C is ecotropic and does not replicate on human cells. The major differences between the classes is in the receptor binding domain of the env protein and the long terminal repeats (LTRs) that influence the replication of each class. PERV-A and PERV-B display LTRs that have repeats in the U3 region. However, PERV-A and PERV-C show repeatless LTRs. Researchers found that PERVs in culture actively adapted to the repeat structure of their LTR in order to match the best replication performance a host cell could perform. At the end of their study, researchers concluded that repeatless PERV LTR evolved from the repeat-harboring LTR. This was likely to have occurred from insertional mutation and was proven through use of data on LTR and env/Env. It is thought that the generation of repeatless LTRs could be reflective of an adaptation process of the virus, changing from an exogenous to an endogenous lifestyle.[48]

A clinical trial study performed in 1999 sampled 160 patients who were treated with different living pig tissues and observed no evidence of a persistent PERV infection in 97% of the patients for whom a sufficient amount of DNA was available to PCR for amplification of PERV sequences. This study stated that retrospective studies are limited to find the true incidence of infection or associated clinical symptoms, however. It suggested using closely monitored prospective trials, which would provide a more complete and detailed evaluation of the possible cross-species PERV transmission and a comparison of the PERV.[49]

Human endogenous retroviruses
Human endogenous retroviruses (HERV) proviruses comprise a significant part of the human genome, with approximately 98,000 ERV elements and fragments making up 5–8%.[1] According to a study published in 2005, no HERVs capable of replication had been identified; all appeared to be defective, containing major deletions or nonsense mutations. This is because most HERVs are merely traces of original viruses, having first integrated millions of years ago. An analysis of HERV integrations is ongoing as part of the 100,000 genomes project.[50]

Human endogenous retroviruses were discovered by accident using a couple of different experiments. Human genomic libraries were screened under low-stringency conditions using probes from animal retroviruses, allowing the isolation and characterization of multiple, though defective, proviruses, that represented various families. Another experiment depended on oligonucleotides with homology to viral primer binding sites.[1]

HERVs are classified based on their homologies to animal retroviruses. Families belong to Class I are similar in sequence to mammalian type C retroviruses. Families belonging to Class II show homology to mammalian type B and D retroviruses. For both classes, if homologies appear well conserved in the gag, pol, and env gene, they are grouped into a superfamily. There more Class I families known to exist.[1]

There are two proposals for how HERVs became fixed in the human genome. The first assumes that sometime during human evolution, exogenous progenitors of HERV inserted themselves into germ line cells and then replicated along with the host's genes using and exploiting the host's cellular mechanisms. Because of their distinct genomic structure, HERVs were subjected to many rounds of amplification and transposition, which lead to a widespread distribution of retroviral DNA. The second hypothesis claims the continuous evolution of retro-elements from more simple structured ancestors.[1]

Nevertheless, one family of viruses has been active since the divergence of humans and chimpanzees. This family, termed HERV-K (HML2), makes up less than 1% of HERV elements but is one of the most studied. There are indications it has even been active in the past few hundred thousand years, e.g., some human individuals carry more copies of HML2 than others.[51] Traditionally, age estimates of HERVs are performed by comparing the 5' and 3' LTR of a HERV; however, this method is only relevant for full-length HERVs. A recent method, called cross-sectional dating,[52] uses variations within a single LTR to estimate the ages of HERV insertions. This method is more precise in estimating HERV ages and can be used for any HERV insertions. Cross-sectional dating has been used to suggest that two members of HERV-K(HML2), HERV-K106 and HERV-K116, were active in the last 800,000 years and that HERV-K106 may have infected modern humans 150,000 years ago.[53] However, the absence of known infectious members of the HERV-K(HML2) family, and the lack of elements with a full coding potential within the published human genome sequence, suggests to some that the family is less likely to be active at present. In 2006 and 2007, researchers working independently in France and the US recreated functional versions of HERV-K(HML2).[54][55]

MER41.AIM2 is an HERV that regulates the transcription of AIM2 (Absent in Melanoma 2) which encodes for a sensor of foreign cytosolic DNA. This acts as a binding site for AIM2, meaning that it is necessary for the transcription of AIM2. Researchers had shown this by deleting MER41.AIM2 in HeLa cells using CRISPR/Cas9, leading to an undetectable transcript level of AIM2 in modified HeLa cells. The control cells, which still contained the MER41.AIM2 ERV, were observed with normal amounts of AIM2 transcript. In terms of immunity, researchers concluded that MER41.AIM2 is necessary for an inflammatory response to infection.[56]

Immunological studies have shown some evidence for T cell immune responses against HERVs in HIV-infected individuals.[57] The hypothesis that HIV induces HERV expression in HIV-infected cells led to the proposal that a vaccine targeting HERV antigens could specifically eliminate HIV-infected cells. The potential advantage of this novel approach is that, by using HERV antigens as surrogate markers of HIV-infected cells, it could circumvent the difficulty inherent in directly targeting notoriously diverse and fast-mutating HIV antigens.[57]

There are a few classes of human endogenous retroviruses that still have intact open reading frames. For example, the expression of HERV-K, a biologically active family of HERV, produces proteins found in placenta. Furthermore, the expression of the envelope genes of HERV-W (ERVW-1)and HERV-FRD (ERVFRD-1) produces syncytins which are important for the generation of the syncytiotrophoblast cell layer during placentogenesis by inducing cell-cell fusion.[58] The HUGO Gene Nomenclature Committee (HGNC) approves gene symbols for transcribed human ERVs.[59]

Techniques for characterizing ERVs
Whole genome sequencing
Example: A porcine ERV (PERV) Chinese-born minipig isolate, PERV-A-BM, was sequenced completely and along with different breeds and cell lines in order to understand its genetic variation and evolution. The observed number of nucleotide substitutions and among the different genome sequences helped researchers determine an estimate age that PERV-A-BM was integrated into its host genome, which was found to be of an evolutionary age earlier than the European-born pigs isolates.[47]

Chromatin Immunoprecipitation with sequencing (ChIP-seq)
This technique is used to find histone marks indicative of promoters and enhancers, which are binding sites for DNA proteins, and repressed regions and trimethylation.[30] DNA methylation has been shown to be vital to maintain silencing of ERVs in mouse somatic cells, while histone marks are vital for the same purpose in embryonic stem cells (ESCs) and early embryogenesis.[5]

Applications
Constructing phylogenies
Because most HERVs have no function, are selectively neutral, and are very abundant in primate genomes, they easily serve as phylogenetic markers for linkage analysis. They can be exploited by comparing the integration site polymorphisms or the evolving, proviral, nucleotide sequences of orthologs. To estimate when integration occurred, researchers used distances from each phylogenetic tree to find the rate of molecular evolution at each particular locus. It is also useful that ERVs are rich in many species genomes (i.e. plants, insects, mollusks, fish, rodents, domestic pets, and livestock) because its application can be used to answer a variety of phylogenetic questions.[7]

Designating the age of provirus and the time points of species separation events
This is accomplished by comparing the different HERV from different evolutionary periods. For example, this study was done for different hominoids, which ranged from humans to apes and to monkeys. This is difficult to do with PERV because of the large diversity present.[48]

Further research
Epigenetic variability
Researchers could analyze individual epigenomes and transcriptomes to study the reactivation of dormant transposable elements through epigenetic release and their potential associations with human disease and exploring the specifics of gene regulatory networks.[5]

Immunological problems of xenotransplantation
Little is known about an effective way to overcoming hyperacute rejection (HAR), which follows the activation of complement initiated by xenoreactive antibodies recognizing galactosyl-alpha1–3galatosyl (alpha-Gal) antigens on the donor epithelium.[44]

Risk factors of HERVs in gene therapy
Because retroviruses are able to recombine with each other and with other endogenous DNA sequences, it would be beneficial for gene therapy to explore the potential risks HERVs can cause, if any. Also, this ability of HERVs to recombine can be manipulated for site-directed integration by including HERV sequences in retroviral vectors.[1]

HERV gene expression
Researchers believe that RNA and proteins encoded for by HERV genes should continue to be explored for putative function in cell physiology and in pathological conditions. This would make sense to examine in order to more deeply define the biological significance of protein's synthesized.

 

Retrowirusy endogenne – są to retrowirusy, które przed milionami lat zainfekowały pierwotne komórki rozrodcze człowieka i innych kręgowców. Dzięki odwrotnej transkryptazie, w postaci DNA włączyły się na stałe do materiału genetycznego organizmu zainfekowanego. Przez miliony lat na skutek licznych mutacji oraz kolejnych infekcji doszło do zwielokrotnienia genomu wirusów, przez co stanowi obecnie znaczną część genomu człowieka jak i innych kręgowców, lecz większość z nich jest uszkodzona i zupełnie nieaktywna.

Sekwencje pochodzenia retrowirusowego stanowią około 8% ludzkiego genomu[1]. Przeważająca większość ludzkich retrowirusów endogennych (HERV – ang. Human Endogenous RetroVirus) jest nieaktywna. Najmłodszą rodziną HERV są retrowirusy HERV-K. Na podstawie analizy sekwencji HERV-K udało się odtworzyć aktywnego wirusa[2][3].

 

Prions are misfolded proteins with the ability to transmit their misfolded shape onto normal variants of the same protein. They characterize several fatal and transmissible neurodegenerative diseases in humans and many other animals.[1] It is not known what causes the normal protein to misfold, but the abnormal three-dimensional structure is suspected of conferring infectious properties, collapsing nearby protein molecules into the same shape. The word prion derives from “proteinaceous infectious particle”.[2][3][4] The hypothesized role of a protein as an infectious agent stands in contrast to all other known infectious agents such as viruses, bacteria, fungi and parasites, all of which contain nucleic acids (DNA, RNA or both).

Prion variants of the prion protein (PrP), whose specific function is uncertain, are hypothesized as the cause of transmissible spongiform encephalopathies (TSEs),[5] including scrapie in sheep, chronic wasting disease (CWD) in deer, bovine spongiform encephalopathy (BSE) in cattle (commonly known as “mad cow disease”) and Creutzfeldt-Jakob disease (CJD) in humans. All known prion diseases in mammals affect the structure of the brain or other neural tissue; all are progressive, have no known effective treatment and are always fatal.[6] Until 2015, all known mammalian prion diseases were considered to be caused by the prion protein (PrP), however in 2015 multiple system atrophy (MSA) was found to be transmissible and was hypothesized to be caused by a prion form of alpha-synuclein.[7]

Prions form abnormal aggregates of proteins called amyloids, which accumulate in infected tissue and are associated with tissue damage and cell death.[8] Amyloids are also responsible for several other neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.[9] Prion aggregates are stable, and this structural stability means that prions are resistant to denaturation by chemical and physical agents: they cannot be destroyed by ordinary disinfection or cooking. This makes disposal and containment of these particles difficult.

A prion disease is a type of proteopathy, or disease of structurally abnormal proteins. In humans, prions are believed to be the cause of Creutzfeldt-Jakob disease (CJD), its variant (vCJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), fatal familial insomnia (FFI) and kuru.[2] There is also evidence suggesting prions may play a part in the process of Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS), and these have been termed prion-like diseases.[10][11][12][13] Several yeast proteins have also been identified as having prionogenic properties.[14][15] Prion replication is subject to epimutation and natural selection just as for other forms of replication, and their structure varies slightly between species.[16]

Recent scientific observations show the need to refine the prion hypothesis.[17] Synthetic prions, created in the laboratory independent of any biological source, have little or no ability to cause infection with TSEs; however, when synthetic prions are administered in combination with cofactors, such as phosphatidylethanolamine and RNA molecules, this can transmit TSEs.[18] It has also been shown that scrapie and Creutzfeldt-Jakob disease may require agent-specific nucleic acids for transmission of infection.[19] Most recently, it was shown that mice with severe combined immunodeficiency do not develop scrapie following inoculation with brain tissue from animals infected with scrapie, suggesting that either the role of immunity in prion pathogenesis is incompletely understood or that there is some other flaw in current understanding of prion pathophysiology.[20]

Contents
1 Prion protein
1.1 Discovery
1.2 Structure
1.3 Normal function PrP
2 Prion replication mechanism
3 Prion diseases and their transmission properties
3.1 Transmission
3.2 Sterilization
4 Fungi
5 Potential treatments and diagnosis
6 Role of prions in transmissible spongiform encephalopathies
6.1 Prion hypothesis
6.2 Heavy metal poisoning hypothesis
6.3 Viral hypothesis
6.4 Virino hypothesis
6.5 Spiroplasma hypothesis
6.6 Acinetobacter-autoimmunity hypothesis
7 Role of prions in other diseases
7.1 Role in neurodegenerative disease
8 Etymology and pronunciation
9 See also
10 References
11 Further reading
12 External links
12.1 General
12.2 Reports and committees
12.3 Genetics
12.4 Research
12.5 Other
Prion protein
See also: Major Prion Protein (PRNP)
Discovery
In the 1950s, Carleton Gajdusek began research which eventually showed that kuru could be transmitted to chimpanzees by what was possibly a new infectious agent, work for which he eventually won the 1976 Nobel prize. During the 1960s, two London-based researchers, radiation biologist Tikvah Alper and biophysicist John Stanley Griffith, developed the hypothesis that the transmissible spongiform encephalopathies are caused by an infectious agent consisting solely of proteins.[21][22] Earlier investigations by E.J. Field into scrapie and kuru had found evidence for the transfer of pathologically inert polysaccharides that only become infectious post-transfer, in the new host.[23][24] Alper and Griffith wanted to account for the discovery that the mysterious infectious agent causing the diseases scrapie and Creutzfeldt-Jakob disease resisted ionizing radiation.[25] (A single ionizing “hit” normally destroys an entire infectious particle, and the dose needed to hit half the particles depends on the size of the particles. Empirical results of ionizing doses applied to the unknown infectious substance evidenced an infectious particle size too small to be a viral mechanism.) In his paper, entitled “Self-replication and Scrapie”, Griffith proposed three ways in which a protein could be a pathogen. In the first hypothesis, he suggested that if the protein is the product of a normally suppressed gene, and introducing the protein could induce the gene's expression, that is, wake the dormant gene up, then the result would be a process indistinguishable from replication, as the gene's expression would produce the protein, which would then go wake the gene up in other cells. His second hypothesis forms the basis of the modern prion theory, and proposed that an abnormal form of a cellular protein can convert normal proteins of the same type into its abnormal form, thus leading to replication. His third hypothesis proposed that the agent could be an antibody if the antibody was its own target antigen, as such an antibody would result in more and more antibody being produced against itself. However, Griffith acknowledged that this third hypothesis was unlikely to be true due to the lack of a detectable immune response.[26]

Francis Crick recognized the potential significance of the Griffith protein-only hypothesis for scrapie propagation in the second edition of his “Central dogma of molecular biology” (1970): While asserting that the flow of sequence information from protein to protein, or from protein to RNA and DNA was “precluded”, he noted that Griffith's hypothesis was a potential contradiction (although it was not so promoted by Griffith).[27] The revised hypothesis was later formulated, in part, to accommodate reverse transcription (which both Howard Temin and David Baltimore discovered in 1970).[citation needed]

In 1982, Stanley B. Prusiner of the University of California, San Francisco announced that his team had purified the hypothetical infectious protein, which did not appear to be present in healthy hosts, though they did not manage to isolate the protein until two years after Prusiner's announcement.[28][29] The protein was named a prion, for “Proteinacious infectious particle”, taken from the words protein and infection. When the prion was discovered, Griffith's first hypothesis, that the protein was the product of a normally silent gene was favored by many. It was subsequently discovered, however, that the same protein exists in normal hosts but in different form. Following the discovery of the same protein in different form in uninfected individuals, the specific protein that the prion was composed of was named the Prion Protein (PrP), and Griffith's second hypothesis that an abnormal form of a host protein can convert other proteins of the same type into its abnormal form, became the dominant theory.[26] Prusiner won the Nobel Prize in Physiology or Medicine in 1997 for his research into prions.[30]

Structure
See also: PRNP § Structure
The protein that prions are made of (PrP) is found throughout the body, even in healthy people and animals. However, PrP found in infectious material has a different structure and is resistant to proteases, the enzymes in the body that can normally break down proteins. The normal form of the protein is called PrPC, while the infectious form is called PrPSc – the C refers to 'cellular' PrP, while the Sc refers to 'scrapie', the prototypic prion disease, occurring in sheep.[31] While PrPC is structurally well-defined, PrPSc is certainly polydisperse and defined at a relatively poor level. PrP can be induced to fold into other more-or-less well-defined isoforms in vitro, and their relationship to the form(s) that are pathogenic in vivo is not yet clear.

PrPC
PrPC is a normal protein found on the membranes of cells. It has 209 amino acids (in humans), one disulfide bond, a molecular mass of 35–36 kDa and a mainly alpha-helical structure. Several topological forms exist; one cell surface form anchored via glycolipid and two transmembrane forms.[32] The normal protein is not sedimentable; meaning that it cannot be separated by centrifuging techniques.[33] Its function is a complex issue that continues to be investigated. PrPC binds copper (II) ions with high affinity.[34] The significance of this finding is not clear, but it is presumed to relate to PrP structure or function. PrPC is readily digested by proteinase K and can be liberated from the cell surface in vitro by the enzyme phosphoinositide phospholipase C (PI-PLC), which cleaves the glycophosphatidylinositol (GPI) glycolipid anchor.[35] PrP has been reported to play important roles in cell-cell adhesion and intracellular signaling in vivo, and may therefore be involved in cell-cell communication in the brain.[36]

PrPres
Protease-resistant PrPSc-like protein (PrPres) is the name given to any isoform of PrPc which is structurally altered and converted into a misfolded proteinase K-resistant form in vitro.[37] To model conversion of PrPC to PrPSc in vitro, Saborio et al. rapidly converted PrPC into a PrPres by a procedure involving cyclic amplification of protein misfolding.[38] The term “PrPres” has been made to distinguish between PrPSc, which is isolated from infectious tissue and associated with the transmissible spongiform encephalopathy agent.[39] For example, unlike PrPSc, PrPres may not necessarily be infectious.

PrPSc
Photomicrograph of mouse neurons showing red stained inclusions identified as scrapies prion protein.
Prion protein (stained in red) revealed in a photomicrograph of neural tissue from a scrapie-infected mouse.
The infectious isoform of PrP, known as PrPSc, or simply the prion, is able to convert normal PrPC proteins into the infectious isoform by changing their conformation, or shape; this, in turn, alters the way the proteins interconnect. PrPSc always causes prion disease. Although the exact 3D structure of PrPSc is not known, it has a higher proportion of β-sheet structure in place of the normal α-helix structure.[40] Aggregations of these abnormal isoforms form highly structured amyloid fibers, which accumulate to form plaques. It is unclear as to whether these aggregates are the cause of cell damage or are simply a side-effect of the underlying disease process.[41] The end of each fiber acts as a template onto which free protein molecules may attach, allowing the fiber to grow. Under most circumstances, only PrP molecules with an identical amino acid sequence to the infectious PrPSc are incorporated into the growing fiber.[33] However, rare cross-species transmission is also possible.

Normal function PrP
The physiological function of the prion protein remains poorly understood. While data from in vitro experiments suggest many dissimilar roles, studies on PrP knockout mice have provided only limited information because these animals exhibit only minor abnormalities. In research done in mice, it was found that the cleavage of PrP proteins in peripheral nerves causes the activation of myelin repair in Schwann cells and that the lack of PrP proteins caused demyelination in those cells.[42]

PrP and regulated cell death
MAVS, RIP1, and RIP3 are prion-like proteins found in other parts of the body. They also polymerise into filamentous amyloid fibers which initiate regulated cell death in the case of a viral infection to prevent the spread of virions to other, surrounding cells.[43]

PrP and long-term memory
A review of evidence in 2005 suggested that PrP may have a normal function in maintenance of long-term memory.[44] As well, a 2004 study found that mice lacking genes for normal cellular PrP protein show altered hippocampal long-term potentiation.[45][46] A recent study that might explain why this is found that neuronal protein CPEB has a similar genetic sequence to yeast prion proteins. The prion-like formation of CPEB is essential for maintaining long-term synaptic changes associated with long term memory formation.[47]

PrP and stem cell renewal
A 2006 article from the Whitehead Institute for Biomedical Research indicates that PrP expression on stem cells is necessary for an organism's self-renewal of bone marrow. The study showed that all long-term hematopoietic stem cells express PrP on their cell membrane and that hematopoietic tissues with PrP-null stem cells exhibit increased sensitivity to cell depletion.[48]

PrP and innate immunity
There is some evidence that PrP may play a role in innate immunity, as the expression of PRNP, the PrP gene, is upregulated in many viral infections and PrP has antiviral properties against many viruses, including HIV.[49]

Prion replication mechanism

Heterodimer model of prion propagation

Fibril model of prion propagation.
The first hypothesis that tried to explain how prions replicate in a protein-only manner was the heterodimer model.[50] This model assumed that a single PrPSc molecule binds to a single PrPC molecule and catalyzes its conversion into PrPSc. The two PrPSc molecules then come apart and can go on to convert more PrPC. However, a model of prion replication must explain both how prions propagate, and why their spontaneous appearance is so rare. Manfred Eigen showed that the heterodimer model requires PrPSc to be an extraordinarily effective catalyst, increasing the rate of the conversion reaction by a factor of around 1015.[51] This problem does not arise if PrPSc exists only in aggregated forms such as amyloid, where cooperativity may act as a barrier to spontaneous conversion. What is more, despite considerable effort, infectious monomeric PrPSc has never been isolated.

An alternative model assumes that PrPSc exists only as fibrils, and that fibril ends bind PrPC and convert it into PrPSc. If this were all, then the quantity of prions would increase linearly, forming ever longer fibrils. But exponential growth of both PrPSc and of the quantity of infectious particles is observed during prion disease.[52][53][54] This can be explained by taking into account fibril breakage.[55] A mathematical solution for the exponential growth rate resulting from the combination of fibril growth and fibril breakage has been found.[56] The exponential growth rate depends largely on the square root of the PrPC concentration.[56] The incubation period is determined by the exponential growth rate, and in vivo data on prion diseases in transgenic mice match this prediction.[56] The same square root dependence is also seen in vitro in experiments with a variety of different amyloid proteins.[57]

The mechanism of prion replication has implications for designing drugs. Since the incubation period of prion diseases is so long, an effective drug does not need to eliminate all prions, but simply needs to slow down the rate of exponential growth. Models predict that the most effective way to achieve this, using a drug with the lowest possible dose, is to find a drug that binds to fibril ends and blocks them from growing any further.[58]

Prion diseases and their transmission properties
Main article: Transmissible spongiform encephalopathy
Diseases caused by prions
Affected animal(s) Disease
Sheep, Goat Scrapie[59]
Cattle Bovine spongiform encephalopathy (BSE), mad cow disease[59]
Camel [60] Camel spongiform encephalopathy (CSE)
Mink[59] Transmissible mink encephalopathy (TME)
White-tailed deer, elk, mule deer, moose[59] Chronic wasting disease (CWD)
Cat[59] Feline spongiform encephalopathy (FSE)
Nyala, Oryx, Greater Kudu[59] Exotic ungulate encephalopathy (EUE)
Ostrich[61] Spongiform encephalopathy
(Has not been shown to be transmissible.)
Human Creutzfeldt-Jakob disease (CJD)[59]
Iatrogenic Creutzfeldt-Jakob disease (iCJD)
Variant Creutzfeldt-Jakob disease (vCJD)
Familial Creutzfeldt-Jakob disease (fCJD)
Sporadic Creutzfeldt-Jakob disease (sCJD)
Gerstmann-Sträussler-Scheinker syndrome (GSS)[59]
Fatal familial insomnia (FFI)[62]
Kuru[59]
Familial spongiform encephalopathy[63]
Until 2015 all known mammalian prion diseases were considered to be caused by the prion protein, PrP; in 2015 multiple system atrophy was found to be transmissible and was hypothesized to be caused by a new prion, the misfolded form of a protein called alpha-synuclein.[7] The endogenous, properly folded form of the prion protein is denoted PrPC (for Common or Cellular), whereas the disease-linked, misfolded form is denoted PrPSc (for Scrapie), after one of the diseases first linked to prions and neurodegeneration.[33][64] The precise structure of the prion is not known, though they can be formed by combining PrPC, polyadenylic acid, and lipids in a protein misfolding cyclic amplification (PMCA) reaction.[65] Proteins showing prion-type behavior are also found in some fungi, which has been useful in helping to understand mammalian prions. Fungal prions do not appear to cause disease in their hosts.[66]

Prions cause neurodegenerative disease by aggregating extracellularly within the central nervous system to form plaques known as amyloid, which disrupt the normal tissue structure. This disruption is characterized by “holes” in the tissue with resultant spongy architecture due to the vacuole formation in the neurons.[67] Other histological changes include astrogliosis and the absence of an inflammatory reaction.[68] While the incubation period for prion diseases is relatively long (5 to 20 years), once symptoms appear the disease progresses rapidly, leading to brain damage and death.[69] Neurodegenerative symptoms can include convulsions, dementia, ataxia (balance and coordination dysfunction), and behavioural or personality changes.

All known prion diseases are untreatable and fatal.[70] However, a vaccine developed in mice may provide insight into providing a vaccine to resist prion infections in humans.[71] Additionally, in 2006 scientists announced that they had genetically engineered cattle lacking a necessary gene for prion production – thus theoretically making them immune to BSE,[72] building on research indicating that mice lacking normally occurring prion protein are resistant to infection by scrapie prion protein.[73] In 2013, a study revealed that 1 in 2,000 people in the United Kingdom might harbour the infectious prion protein that causes vCJD.[74]

Many different mammalian species can be affected by prion diseases, as the prion protein (PrP) is very similar in all mammals.[75] Due to small differences in PrP between different species it is unusual for a prion disease to transmit from one species to another. The human prion disease variant Creutzfeldt-Jakob disease, however, is thought to be caused by a prion that typically infects cattle, causing bovine spongiform encephalopathy and is transmitted through infected meat.[76]

Transmission
It has been recognized that prion diseases can arise in three different ways: acquired, familial, or sporadic.[77] It is often assumed that the diseased form directly interacts with the normal form to make it rearrange its structure. One idea, the “Protein X” hypothesis, is that an as-yet unidentified cellular protein (Protein X) enables the conversion of PrPC to PrPSc by bringing a molecule of each of the two together into a complex.[78]

Current research suggests that the primary method of infection in animals is through ingestion. It is thought that prions may be deposited in the environment through the remains of dead animals and via urine, saliva, and other body fluids. They may then linger in the soil by binding to clay and other minerals.[79]

A University of California research team, led by Nobel Prize winner Stanley Prusiner, has provided evidence for the theory that infection can occur from prions in manure.[80] And, since manure is present in many areas surrounding water reservoirs, as well as used on many crop fields, it raises the possibility of widespread transmission. It was reported in January 2011 that researchers had discovered prions spreading through airborne transmission on aerosol particles, in an animal testing experiment focusing on scrapie infection in laboratory mice.[81] Preliminary evidence supporting the notion that prions can be transmitted through use of urine-derived human menopausal gonadotropin, administered for the treatment of infertility, was published in 2011.[82]

Prions in plants
In 2015, researchers at The University of Texas Health Science Center at Houston found that plants can be a vector for prions. When researchers fed hamsters grass that grew on ground where a deer that died with chronic wasting disease (CWD) was buried, the hamsters became ill with CWD, suggesting that prions can bind to plants, which then take them up into the leaf and stem structure, where they can be eaten by herbivores, thus completing the cycle. It is thus possible that there is a progressively accumulating number of prions in the environment.[83][84]

Sterilization
Infectious particles possessing nucleic acid are dependent upon it to direct their continued replication. Prions, however, are infectious by their effect on normal versions of the protein. Sterilizing prions, therefore, requires the denaturation of the protein to a state in which the molecule is no longer able to induce the abnormal folding of normal proteins. In general, prions are quite resistant to proteases, heat, ionizing radiation, and formaldehyde treatments,[85] although their infectivity can be reduced by such treatments. Effective prion decontamination relies upon protein hydrolysis or reduction or destruction of protein tertiary structure. Examples include sodium hypochlorite, sodium hydroxide, and strongly acidic detergents such as LpH.[86] 134 °C (274 °F) for 18 minutes in a pressurized steam autoclave has been found to be somewhat effective in deactivating the agent of disease.[87][88] Ozone sterilization is currently being studied as a potential method for prion denaturation and deactivation.[89] Renaturation of a completely denatured prion to infectious status has not yet been achieved; however, partially denatured prions can be renatured to an infective status under certain artificial conditions.[90]

The World Health Organization recommends any of the following three procedures for the sterilization of all heat-resistant surgical instruments to ensure that they are not contaminated with prions:

Immerse in 1N sodium hydroxide and place in a gravity-displacement autoclave at 121 °C for 30 minutes; clean; rinse in water; and then perform routine sterilization processes.
Immerse in 1N sodium hypochlorite (20,000 parts per million available chlorine) for 1 hour; transfer instruments to water; heat in a gravity-displacement autoclave at 121 °C for 1 hour; clean; and then perform routine sterilization processes.
Immerse in 1N sodium hydroxide or sodium hypochlorite (20,000 parts per million available chlorine) for 1 hour; remove and rinse in water, then transfer to an open pan and heat in a gravity-displacement (121 °C) or in a porous-load (134 °C) autoclave for 1 hour; clean; and then perform routine sterilization processes.[91]
Fungi
Main article: Fungal prion
In yeast, protein refolding to the prion configuration is assisted by chaperone proteins such as Hsp104.[15] All known prions induce the formation of an amyloid fold, in which the protein polymerises into an aggregate consisting of tightly packed beta sheets. Amyloid aggregates are fibrils, growing at their ends, and replicate when breakage causes two growing ends to become four growing ends. The incubation period of prion diseases is determined by the exponential growth rate associated with prion replication, which is a balance between the linear growth and the breakage of aggregates.[56]

Fungal proteins exhibiting templated conformational change[further explanation needed] were discovered in the yeast Saccharomyces cerevisiae by Reed Wickner in the early 1990s. For their mechanistic similarity to mammalian prions, they were termed yeast prions. Subsequent to this, a prion has also been found in the fungus Podospora anserina. These prions behave similarly to PrP, but, in general, are nontoxic to their hosts. Susan Lindquist's group at the Whitehead Institute has argued some of the fungal prions are not associated with any disease state, but may have a useful role; however, researchers at the NIH have also provided arguments suggesting that fungal prions could be considered a diseased state.[92] There is mounting evidence that fungal proteins have evolved specific functions that are beneficial to the microorganism that enhance their ability to adapt to their diverse environments.[93]

As of 2012, there are eight known prion proteins in fungi, seven in Saccharomyces cerevisiae (Sup35, Rnq1, Ure2, Swi1, Mot3, Cyc8, and Mod5) and one in Podospora anserina (HET-s).[contradictory] The article that reported the discovery of a prion form, the Mca1 protein, was retracted due to the fact that the data could not be reproduced.[94] Notably, most of the fungal prions are based on glutamine/asparagine-rich sequences, with the exception of HET-s and Mod5.

Research into fungal prions has given strong support to the protein-only concept, since purified protein extracted from cells with a prion state has been demonstrated to convert the normal form of the protein into a misfolded form in vitro, and in the process, preserve the information corresponding to different strains of the prion state. It has also shed some light on prion domains, which are regions in a protein that promote the conversion into a prion. Fungal prions have helped to suggest mechanisms of conversion that may apply to all prions, though fungal prions appear distinct from infectious mammalian prions in the lack of cofactor required for propagation. The characteristic prion domains may vary between species – e.g., characteristic fungal prion domains are not found in mammalian prions.

Fungal prions
Protein Natural host Normal function Prion state Prion phenotype Year identified
Ure2p Saccharomyces cerevisiae Nitrogen catabolite repressor [URE3] Growth on poor nitrogen sources 1994
Sup35p S. cerevisiae Translation termination factor [PSI+] Increased levels of nonsense suppression 1994
HET-S Podospora anserina Regulates heterokaryon incompatibility [Het-s] Heterokaryon formation between incompatible strains
Rnq1p S. cerevisiae Protein template factor [RNQ+], [PIN+] Promotes aggregation of other prions
Swi1 S. cerevisiae Chromatin remodeling [SWI+] Poor growth on some carbon sources 2008
Cyc8 S. cerevisiae Transcriptional repressor [OCT+] Transcriptional derepression of multiple genes 2009
Mot3 S. cerevisiae Nuclear transcription factor [MOT3+] Transcriptional derepression of anaerobic genes 2009
Sfp1 S. cerevisiae Putative transcription factor [ISP+] Antisuppression 2010[95][contradictory]
Potential treatments and diagnosis
Advancements in computer modeling have allowed scientists to identify compounds that can treat prion-caused diseases, such as one compound found to bind a cavity in the PrPC and stabilize the conformation, reducing the amount of harmful PrPSc.[96]

Antiprion antibodies capable of crossing the blood-brain-barrier and targeting cytosolic prion protein (an otherwise major obstacle in prion therapeutics) have been described.[97]

In the last decade, some progress dealing with ultra-high-pressure inactivation of prion infectivity in processed meat has been reported.[98]

In 2011, it was reported that prions could be degraded by lichens.[99] Astemizole has been found to have anti-prion activity.[100] Another type of chemical that may be effective against prion infection is the luminescent conjugated polythiophenes, fluorescent compounds that are often used to stain tissue samples. In a 2015 study, it was found that that when they injected mice with a prion disease and then with polythiophenes, the mice survived 80% longer than the control mice that were injected only with the prion disease.[101]

There continues to be a practical problem with diagnosis of prion diseases, including BSE and CJD. They have an incubation period of months to decades, during which there are no symptoms, even though the pathway of converting the normal brain PrP protein into the toxic, disease-related PrPSc form has started. At present, there is virtually no way to detect PrPSc reliably except by examining the brain using neuropathological and immunohistochemical methods after death. Accumulation of the abnormally folded PrPSc form of the PrP protein is a characteristic of the disease, but it is present at very low levels in easily accessible body fluids like blood or urine. Researchers have tried to develop methods to measure PrPSc, but there are still no fully accepted methods for use in materials such as blood.[citation needed]

In 2010, a team from New York described detection of PrPSc even when initially present at only one part in a hundred billion (10−11) in brain tissue. The method combines amplification with a novel technology called surround optical fiber immunoassay (SOFIA) and some specific antibodies against PrPSc. After amplifying and then concentrating any PrPSc, the samples are labelled with a fluorescent dye using an antibody for specificity and then finally loaded into a micro-capillary tube. This tube is placed in a specially constructed apparatus so that it is totally surrounded by optical fibres to capture all light emitted once the dye is excited using a laser.[102][103]

The RT-QuIC assay, a microplate reader-based prion detection method which uses as reagents normally folded prions, fluorescently labelled so that they “light up” when they are misfolded; samples suspected of containing misfolded prions are added and misfolded reagents can be detected by standard fluorescence detection methods.[104][105][106] The Center for Disease Control and Prevention includes a positive RT-QuIC result in its diagnostic criteria for the probable diagnosis of sCJD.[107]

A 2015 study found that a naturally occurring variant of the human prion protein in transgenic mice protected them against kuru and CJD.[108]

SGI-1027 and related compounds were identified as a novel class of potential anti-prion agents that preferentially function through direct interaction with PrPC.[109]

Role of prions in transmissible spongiform encephalopathies
The cause of the transmissible spongiform encephalopathies (TSE) is currently unknown, but the diseases are known to be associated with prions. Whether prions cause TSEs or are the result of infection with another agent such as a virus is a matter of debate by a minority of scientists. The following are some hypotheses.

Prion hypothesis
The prion hypothesis states that the main component of the TSE agent is composed of a misfolded protein. The prion hypothesis can be divided into two sub-hypotheses: the protein-only hypothesis, and the multi-component hypothesis.

Protein-only hypothesis
Prior to the discovery of prions, it was thought that all pathogens used nucleic acids to direct their replication. The “protein-only hypothesis” states that a protein structure can replicate without the use of nucleic acids. This was initially controversial as it contradicts the central dogma of molecular biology, which describes nucleic acid as the central form of replicative information.

Evidence in favor of a protein-only hypothesis includes:[41]

Infectivity titre in TSEs roughly correlates with prion amyloid (PrPSc) titre, however, prion amyloid is undetectable in approximately 10% of CJD cases.[110]
No virus particles, bacteria, or fungi have been conclusively associated with prion diseases, although virus-like particles and Spiroplasma-like inclusions can be detected in some TSE cases, but not in controls (uninfected individuals).[111][112]
No nucleic acid has been conclusively associated with infectivity; agent is resistant to ultraviolet radiation and nucleases, although in 2016, studies have suggested that the agent can be destroyed by nucleases under certain situations and that part of the resistance to nucleases and radiation may be that byproducts from degenerating neurons may help protect a nucleic acid.[113]
No immune or inflammatory response to infection.
PrPSc experimentally transmitted between one species and another results in PrPSc with the amino-acid sequence of the recipient species, suggesting that nucleic acid-mediated replication of the donor agent does not occur.[114]
Familial prion disease occurs in families with a mutation in the PrP gene, and mice with PrP mutations develop prion disease despite controlled conditions where transmission is prevented. These mice can then transmit the disease to healthy, wild type mice, suggesting that mice with PrP mutations spontaneously generate infectivity.
Animals lacking PrPC do not contract prion disease.
Genetic factors
A gene for the normal protein has been identified: the PRNP gene.[115] In all inherited cases of prion disease, there is a mutation in the PRNP gene. Many different PRNP mutations have been identified and these proteins are more likely to fold into abnormal prion.[116] Although this discovery puts a hole in the general prion hypothesis, that prions can aggregate only proteins of identical amino acid make-up. These mutations can occur throughout the gene. Some mutations involve expansion of the octapeptide repeat region at the N-terminal of PrP. Other mutations that have been identified as a cause of inherited prion disease occur at positions 102, 117 & 198 (GSS), 200, 210 & 232 (CJD) and 178 (fatal familial insomnia, FFI). The cause of prion disease can be sporadic, genetic, or infectious, or a combination of these factors.[117] For example, to have scrapie, both an infectious agent and a susceptible genotype must be present.[116]

Multi-component hypothesis
Despite much effort, significant titers of prion infectivity have never been produced by refolding pure PrP molecules, raising doubt about the validity of the protein-only hypothesis. In addition, the protein-only hypothesis fails to provide a molecular explanation for the ability of prion strains to target specific areas of the brain in distinct patterns. These shortcomings, along with additional experimental data, have given rise to the “multi-component” or “cofactor variation” hypothesis.[118]

In 2007, biochemist Surachai Supattapone and his colleagues at Dartmouth College produced purified infectious prions de novo from defined components (PrPC, co-purified lipids, and a synthetic polyanionic molecule).[65] These researchers also showed that the polyanionic molecule required for prion formation was selectively incorporated into high-affinity complexes with PrP molecules, leading them to hypothesize that infectious prions may be composed of multiple host components, including PrP, lipid, and polyanionic molecules, rather than PrPSc alone.[119]

In 2010, Jiyan Ma and colleagues at the Ohio State University produced infectious prions from a recipe of bacterially expressed recombinant PrP, POPG phospholipid, and RNA, further supporting the multi-component hypothesis.[120] This finding is in contrast to studies that found minimally infectious prions produced from recombinant PrP alone.[121][122]

In 2012, Supattapone and colleagues purified the membrane lipid phosphatidylethanolamine as a solitary endogenous cofactor capable of facilitating the formation of high-titer recombinant prions derived from multiple prion strains.[123] They also reported that the cofactor is essential for maintaining the infectious conformation of PrPSc, and that cofactor molecules dictate the strain properties of infectious prions.[124]

Difficulties associated with the prion hypothesis
The following are some of the current difficulties and challenges:[125]

Several different types of PrPSc occur in the brains of animals with scrapie. As PrPSc consist only of peptides, there is no known mechanism by which different prion types can occur.
The mechanism by which the number of PrPSc molecules increases by orders-of-magnitude remains unexplained.
There has been no satisfactory explanation as to how prion peptides with the same amino acid sequence change their 3-dimensional folding structure from an alpha helix to a beta sheet.
The presence of damaged neurologic tissue is consistent with other hypotheses besides a prion.
Inexplicably, mice with severe combined immunodeficiency do not develop scrapie following inoculation with brain tissue from animals infected with scrapie.
Whether prions cause disease or are merely a symptom resulting from a different agent is still a matter of debate and research. The following sections describe several hypotheses: some pertain to the composition of the infectious agent (protein-only, protein with other components, virus, or other), while others pertain to its mechanism of reproduction.

Heavy metal poisoning hypothesis
Reports suggest that imbalance of brain metal homeostasis may be a cause of PrPSc-associated neurotoxicity, though the underlying mechanisms are difficult to explain based on existing information. Proposed hypotheses include a functional role for PrPC in metal metabolism, and loss of this function due to aggregation to the disease-associated PrPSc form as the cause of brain metal imbalance. Other views suggest gain of toxic function by PrPSc due to sequestration of PrPC-associated metals within the aggregates, resulting in the generation of redox-active PrPSc complexes. The physiological implications of some PrPC-metal interactions are known, while others are still unclear. The pathological implications of PrPC-metal interaction include metal-induced oxidative damage, and in some instances conversion of PrPC to a PrPSc-like form.[126]

Viral hypothesis
The protein-only hypothesis has been criticised by those maintaining that the simplest explanation of the evidence to date is viral.[127] For more than a decade, Yale University neuropathologist Laura Manuelidis has been proposing that prion diseases are caused instead by an unidentified slow virus. In January 2007, she and her colleagues published an article reporting to have found a virus in 10%, or less, of their scrapie-infected cells in culture.[128][129] In 2016, Sotirios Botsios and Laura Manuelidis showed evidence that TSE specific nucleic acids may be required for infectious transmission of CJD and scrapie.[19]

Evidence in favor of a viral hypothesis includes:[41]

Strain variation: differences in prion infectivity, incubation, symptomology, and progression among species resembles that seen between viruses, especially RNA viruses
The long incubation and rapid onset of symptoms resembles lentiviruses, such as HIV-induced AIDS
Viral-like particles that do not appear to be composed of PrP have been found in some of the cells of scrapie- or CJD-infected cell lines.[129]
Many viruses, including HIV which needs CD4 and CXCR4, need a receptor to attach to and enter into host cells. The host prion, PrPc may be a receptor protein for an as yet undiscovered TSE virus, explaining why animals lacking host prion do not become infected with experimental prion disease.[17][111]
A prion-like protein, called MAVS, has been shown to misfold as part of the innate immune response against pathogenic viruses,[130][131] similarly the cellular prion, PrPC has been shown to have anti HIV properties,[132] and it is hypothesized that the misfolding of the prion in TSEs may be an antiviral response against an unknown virus.[111]
In 2016, studies have demonstrated susceptibility to nucleases under certain situations:

>99% of infectivity was destroyed, but there was no reduction of prion protein, suggesting the presence of a nucleic acid.[113]
Studies propagating TSE infectivity in cell-free reactions[133] and in purified component chemical reactions[65] is thought to strongly suggest against TSE viral nature. However, some viruses, such as poliovirus, have the ability to replicate in cell-free reactions.[17][134][135]

Virino hypothesis
The 'virino hypothesis' postulates that the TSE agent is a foreign, self replicating nucleic acid or nucleic acid fragment bound to PrP.[136][137]

Spiroplasma hypothesis
Spiroplasma is a cell wall-deficient bacterium related to Mycoplasma, which some think may be the cause of the TSEs. The lack of a cell wall means it is not susceptible to conventional antibiotics such as penicillin, which target cell wall synthesis. Frank O. Bastian of Louisiana State University first discovered Spiroplasma-like inclusions in the brain of a CJD patient during an autopsy in 1979[112] and has hypothesized that this bacterium could possibly be the cause of the TSEs.[110][138][139]

However, as of 2015, with the exception of Spiroplasma mirum strain SMCA causing spongiform microcystic encephalitis in suckling rats, other researchers have been unable to duplicate these findings,[140][141][142] casting doubt on the Spiroplasma hypothesis. In defense of the Spiroplasma hypothesis, Bastian pointed out that Spiroplasma is hard to culture and that strain variation makes it hard to detect certain strains using PCR and other techniques, thus giving a false negative.

Acinetobacter-autoimmunity hypothesis
Acinetobacter is a bacterium which some think is the cause of the TSEs. Mainly because some CJD patients produce antibodies against Acinetobacter calcoaceticus.[143][144]

Role of prions in other diseases
Prion-like domains have been found in a variety of other mammalian proteins. Some of these proteins have been implicated in the ontogeny of age-related neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) a motor neuron disease, frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U), Alzheimer's disease, Parkinson's disease, and Huntington's disease.[145][12][11] They are also implicated in some forms of systemic amyloidosis including AA amyloidosis that develops in humans and animals with inflammatory and infectious diseases such as tuberculosis, Crohn's disease, rheumatoid arthritis, and HIV AIDS. AA amyloidosis, like prion disease, may be transmissible.[146] This has given rise to the 'prion paradigm', where otherwise harmless proteins can be converted to a pathogenic form by a small number of misfolded, nucleating proteins.[147]

The definition of a prion-like domain arises from the study of fungal prions. In yeast, prionogenic proteins have a portable prion domain that is both necessary and sufficient for self-templating and protein aggregation. This has been shown by attaching the prion domain to a reporter protein, which then aggregates like a known prion. Similarly, removing the prion domain from a fungal prion protein inhibits prionogenesis. This modular view of prion behaviour has led to the hypothesis that similar prion domains are present in animal proteins, in addition to PrP.[145] These fungal prion domains have several characteristic sequence features. They are typically enriched in asparagine, glutamine, tyrosine and glycine residues, with an asparagine bias being particularly conducive to the aggregative property of prions. Historically, prionogenesis has been seen as independent of sequence and only dependent on relative residue content. However, this has been shown to be false, with the spacing of prolines and charged residues having been shown to be critical in amyloid formation.[14]

Bioinformatic screens have predicted that over 250 human proteins contain prion-like domains (PrLD). These domains are hypothesized to have the same transmissible, amyloidogenic properties of PrP and known fungal proteins. As in yeast, proteins involved in gene expression and RNA binding seem to be particularly enriched in PrLD's, compared to other classes of protein. In particular, 29 of the known 210 proteins with an RNA recognition motif also have a putative prion domain. Meanwhile, several of these RNA-binding proteins have been independently identified as pathogenic in cases of ALS, FTLD-U, Alzheimer's disease, and Huntington's disease.[148]

Role in neurodegenerative disease
The pathogenicity of prions and proteins with prion-like domains is hypothesized to arise from their self-templating ability and the resulting exponential growth of amyloid fibrils. The presence of amyloid fibrils in patients with degenerative diseases has been well documented. These amyloid fibrils are seen as the result of pathogenic proteins that self-propagate and form highly stable, non-functional aggregates.[148] While this does not necessarily imply a causal relationship between amyloid and degenerative diseases, the toxicity of certain amyloid forms and the overproduction of amyloid in familial cases of degenerative disorders supports the idea that amyloid formation is generally toxic.

Specifically, aggregation of TDP-43, an RNA-binding protein, has been found in ALS/MND patients, and mutations in the genes coding for these proteins have been identified in familial cases of ALS/MND. These mutations promote the misfolding of the proteins into a prion-like conformation. The misfolded form of TDP-43 forms cytoplasmic inclusions in afflicted neurons, and is found depleted in the nucleus. In addition to ALS/MND and FTLD-U, TDP-43 pathology is a feature of many cases of Alzheimer's disease, Parkinson's disease and Huntington's disease. The misfolding of TDP-43 is largely directed by its prion-like domain. This domain is inherently prone to misfolding, while pathological mutations in TDP-43 have been found to increase this propensity to misfold, explaining the presence of these mutations in familial cases of ALS/MND. As in yeast, the prion-like domain of TDP-43 has been shown to be both necessary and sufficient for protein misfolding and aggregation.[145]

Similarly, pathogenic mutations have been identified in the prion-like domains of heterogeneous nuclear riboproteins hnRNPA2B1 and hnRNPA1 in familial cases of muscle, brain, bone and motor neuron degeneration. The wild-type form of all of these proteins show a tendency to self-assemble into amyloid fibrils, while the pathogenic mutations exacerbate this behaviour and lead to excess accumulation.[149]

Etymology and pronunciation
The word prion, coined in 1982 by Stanley B. Prusiner, is a portmanteau derived from protein and infection, hence prion,[150][151] and is short for “proteinaceous infectious particle”,[7] in reference to its ability to self-propagate and transmit its conformation to other proteins.[152] Its main pronunciation is /ˈpriːɒn/ (About this soundlisten),[153][154][155] although /ˈpraɪɒn/, as the homographic name of the bird is pronounced,[155] is also heard.[156] In his 1982 paper introducing the term, Prusiner specified that it be “pronounced pree-on.”[29]

 

Priony (ang. prion, od proteinaceous infectious particle) – białkowe cząsteczki zakaźne[1][2], powstają z występujących powszechnie w wielu organizmach i całkowicie niegroźnych białek. Dopiero w sytuacji, gdy zmieniają one swoją naturalną konformację, stają się białkiem prionowym infekcyjnym.

Spis treści
1 Historia
2 Teoria prionu
3 Choroby prionowe
4 Kontrowersje
5 Priony w drożdżach
6 Zobacz też
7 Przypisy
8 Bibliografia
9 Linki zewnętrzne
Historia
Termin “prion” został wprowadzony do literatury w roku 1982 na łamach Science przez Stanleya Prusinera[3][4]. W tym samym roku wykryto białko prionu (PrP) i stwierdzono korelację między ilością białka a infekcyjnością materiału zakaźnego. Określenie sekwencji białka PrP poprzedziło zidentyfikowanie genu kodującego PrP (u człowieka ma nazwę PRNP)[5].

Teoria prionu
Koncepcja prionów jako czynników etiologicznych zbudowanych wyłącznie z białka (bez kwasów nukleinowych) wymaga przyjęcia całkowicie odmiennego sposobu ich powielania, gdyż nie zawierają one informacji genetycznej. Priony, infekcyjne cząsteczki białka, powodują choroby układu nerwowego zwierząt[4] (m.in. scrapie u owiec i bydła) oraz człowieka (m.in. chorobę Creutzfeldta-Jakoba i kuru). Dużym echem obiło się w 1996 podejrzenie, że chorobą Creutzfeldta-Jacoba ludzie mogą zarażać się poprzez zjedzenie mięsa bydła chorego na BSE (tzw. „szalonych krów”). Zarówno w jednym, jak i drugim przypadku, czynnikiem powodującym chorobę są priony. Za badania nad prionami i sformułowanie rewolucyjnej teorii, że białka miałyby mieć charakter infekcyjny[4], Stanley Prusiner otrzymał w 1997 Nagrodę Nobla z dziedziny medycyny.

Ponieważ niemożliwy jest proces replikowania się cząsteczki białka bez udziału kwasu nukleinowego, zagadką było rozprzestrzenianie się i namnażanie patogenu. Odkrycie genu PRNP u człowieka i analogicznych genów (Prn-p) u większości zwierząt wyższych (wszystkich ssaków, gadów i płazów) przyniosło wniosek, że kodowane przez ten gen białko jest niezbędne w funkcjonowaniu niepoznanych jeszcze fizjologicznych procesów u tych organizmów. Porównanie cząsteczek białek PrP obecnych w tkankach zdrowych i w patologiach, takich jak scrapie, dowiodło, że mają one identyczną strukturę pierwszorzędową, ale różnią się strukturą drugorzędową, co wiąże się z odmiennymi właściwościami fizykochemicznymi. Białko PrP niewywołujące choroby (oznaczane PrPC, C z ang. cellular – komórkowe) posiada trzy α-helisy i dwie tzw. β-nici, natomiast białko PrP o domniemanym patogennym charakterze (oznaczane PrPSc, od scrapie) zawiera przewagę struktury tzw. harmonijki β. Białko PrPC jest całkowicie rozpuszczalne w wodzie, natomiast PrPSc jest nierozpuszczalne (stąd jedynie hipotetyczna jest struktura tego białka – nierozpuszczalność uniemożliwia wykonanie wielu badań analitycznych, np. rentgenografii strukturalnej formy krystalicznej). Najważniejszą tezą teorii prionu sformułowanej przez Prusinera jest, że białko PrPSc wpływa na cząsteczki białka PrPC, zmieniając ich konformację i zaburzając niepoznane jeszcze procesy, w których priony fizjologicznie biorą udział[6]. Białko PrPSc jest trwałe i łatwo zakaża inne komórki, gdzie katalizuje przemianę obecnych tam cząsteczek PrPC w odmianę prionową[7].

Choroby prionowe
Osobny artykuł: Pasażowalne encefalopatie gąbczaste.
Choroby prionowe, czyli zakaźne encefalopatie gąbczaste, to choroby układu nerwowego zwierząt spowodowane nagromadzeniem białek prionowych.

Kontrowersje
Teoria prionu spotykała się od początku z dużym sceptycyzmem, ponieważ występowała przeciwko centralnemu dogmatowi biologii molekularnej – nieodwracalności procesu przejścia informacji genetycznej z kwasu nukleinowego do białek[8]. Wyjaśnienie patogenezy chorób prionowych przy jednoczesnym wykazaniu braku kwasów nukleinowych w materiale zakaźnym spotkało się z niedowierzaniem i eksperymenty te wciąż są powtarzane. Na początku 2007 roku w Proceedings of the National Academy of Sciences ukazała się praca, której autorzy dowodzą obecności małych (25 nm średnicy) wirusopodobnych cząstek w zakaźnym materiale pozbawionym białek PrP, nawiązując do teorii o wirusowym charakterze czynnika scrapie[9].

Priony w drożdżach
W 1997 roku naukowcy odkryli obecność prionów towarzyszących DNA drożdży[10]. Po odwirowaniu DNA z komórek drożdży na dnie probówek z DNA zostawały mętne resztki, które później zidentyfikowano właśnie jako priony. Podczas podziału komórki DNA jest kopiowane, zaś priony ulegają podzieleniu na dwa identyczne białka, które następnie dobudowują sobie drugą część przez przemianę innego białka. Badacze doszli do wniosku, że priony są niezbędne do rozmnażania komórek drożdży[11].

 

Virus classification is the process of naming viruses and placing them into a taxonomic system. Similar to the classification systems used for cellular organisms, virus classification is the subject of ongoing debate and proposals. This is mainly due to the pseudo-living nature of viruses, which is to say they are non-living particles with some chemical characteristics similar to those of life, or non-cellular life. As such, they do not fit neatly into the established biological classification system in place for cellular organisms.

Viruses are mainly classified by phenotypic characteristics, such as morphology, nucleic acid type, mode of replication, host organisms, and the type of disease they cause. The formal taxonomic classification of viruses is the responsibility of the International Committee on Taxonomy of Viruses (ICTV) system, although the Baltimore classification system can be used to place viruses into one of seven groups based on their manner of mRNA synthesis. Specific naming conventions and further classification guidelines are set out by the ICTV.

A catalogue of all the world's known viruses has been proposed; some related preliminary efforts have been accomplished.[1]

Contents
1 Virus species definition
2 ICTV classification
3 Structure-based virus classification
4 Baltimore classification
4.1 DNA viruses
4.2 RNA viruses
4.3 Reverse transcribing viruses
5 Holmes classification
6 LHT System of Virus Classification
7 Subviral agents
7.1 Viroids
7.2 Satellites
7.3 Prions
7.4 Defective interfering particles
8 See also
9 Notes
10 External links
Virus species definition
Species form the basis for any biological classification system. The ICTV had adopted the principle that a virus species is a polythetic class of viruses that constitutes a replicating lineage and occupies a particular ecological niche. In July 2013, the ICTV definition of species changed to state: “A species is a monophyletic group of viruses whose properties can be distinguished from those of other species by multiple criteria.”[2]

ICTV classification
The International Committee on Taxonomy of Viruses began to devise and implement rules for the naming and classification of viruses early in the 1970s, an effort that continues to the present. The ICTV is the only body charged by the International Union of Microbiological Societies with the task of developing, refining, and maintaining a universal virus taxonomy.[3]

The system shares many features with the classification system of cellular organisms, such as taxon structure. However, this system of nomenclature differs from other taxonomic codes on several points. A minor point is that names of orders and families are italicized,[4] unlike in the International Code of Nomenclature for algae, fungi, and plants and International Code of Zoological Nomenclature.

Viral classification starts at the level of realm and continues as follows, with the taxon suffixes given in italics[5]:

Realm (-viria)
Subrealm (-vira)
Kingdom (-viriae)
Subkingdom (-virites)
Phylum (-viricota)
Subphylum (-viricotina)
Class (-viricetes)
Subclass (-viricetidae)
Order (-virales)
Suborder (-virineae)
Family (-viridae)
Subfamily (-virinae)
Genus (-virus)
Subgenus (-virus)
Species
Species names often take the form of [Disease] virus, particularly for higher plants and animals. As of November 2018, only phylum, subphylum, class, order, suborder, family, subfamily, genus, and species are used.

The establishment of an order is based on the inference that the virus families it contains have most likely evolved from a common ancestor. The majority of virus families remain unplaced.

As of 2018, one realm, four incertae sedis orders, 46 incertae sedis families, and three incertae sedis genera are accepted:[6]

Realms: Riboviria

Incertae sedis orders: Caudovirales, Herpesvirales, Ligamenvirales, Ortervirales

Incertae sedis families: Adenoviridae, Alphasatellitidae, Ampullaviridae, Anelloviridae, Ascoviridae, Asfarviridae, Bacilladnaviridae, Baculoviridae, Bicaudaviridae, Bidnaviridae, Circoviridae, Clavaviridae, Corticoviridae, Fuselloviridae, Geminiviridae, Genomoviridae, Globuloviridae, Guttaviridae, Hepadnaviridae, Hytrosaviridae, Inoviridae, Iridoviridae, Lavidaviridae, Marseilleviridae, Microviridae, Mimiviridae, Nanoviridae, Nimaviridae, Nudiviridae, Ovaliviridae, Papillomaviridae, Parvoviridae, Phycodnaviridae, Plasmaviridae, Pleolipoviridae, Polydnaviridae, Polyomaviridae, Portogloboviridae, Poxviridae, Smacoviridae, Sphaerolipoviridae, Spiraviridae, Tectiviridae, Tolecusatellitidae, Tristromaviridae, Turriviridae

Incertae sedis genera: Dinodnavirus, Rhizidiovirus, Salterprovirus

Higher virus taxa span viruses with varying host ranges. The Ortervirales (Groups VI and VII), containing also retroviruses (infecting animals including humans e.g. HIV), retrotransposons (infecting invertebrate animals, plants and eukaryotic microorganisms) and caulimoviruses (infecting plants), are recent additions to the classification system orders.[7][8] Other variations occur between the orders: Nidovirales, for example, are isolated for their differentiation in expressing structural and nonstructural proteins separately.

Structure-based virus classification
It has been suggested that similarity in virion assembly and structure observed for certain viral groups infecting hosts from different domains of life (e.g., bacterial tectiviruses and eukaryotic adenoviruses or prokaryotic Caudovirales and eukaryotic herpesviruses) reflects an evolutionary relationship between these viruses.[9] Therefore, structural relationship between viruses has been suggested to be used as a basis for defining higher-level taxa – structure-based viral lineages – that could complement the existing ICTV classification scheme.[10]

Baltimore classification
Main articles: Baltimore classification and Virus Information Table

The Baltimore Classification of viruses is based on the method of viral mRNA synthesis
Baltimore classification (first defined in 1971) is a classification system that places viruses into one of seven groups depending on a combination of their nucleic acid (DNA or RNA), strandedness (single-stranded or double-stranded), sense, and method of replication. Named after David Baltimore, a Nobel Prize-winning biologist, these groups are designated by Roman numerals. Other classifications are determined by the disease caused by the virus or its morphology, neither of which are satisfactory due to different viruses either causing the same disease or looking very similar. In addition, viral structures are often difficult to determine under the microscope. Classifying viruses according to their genome means that those in a given category will all behave in a similar fashion, offering some indication of how to proceed with further research. Viruses can be placed in one of the seven following groups:[11]

I: dsDNA viruses (e.g. Adenoviruses, Herpesviruses, Poxviruses)
II: ssDNA viruses (+ strand or “sense”) DNA (e.g. Parvoviruses)
III: dsRNA viruses (e.g. Reoviruses)
IV: (+)ssRNA viruses (+ strand or sense) RNA (e.g. Picornaviruses, Togaviruses)
V: (−)ssRNA viruses (− strand or antisense) RNA (e.g. Orthomyxoviruses, Rhabdoviruses)
VI: ssRNA-RT viruses (+ strand or sense) RNA with DNA intermediate in life-cycle (e.g. Retroviruses)
VII: dsDNA-RT viruses DNA with RNA intermediate in life-cycle (e.g. Hepadnaviruses)

Visualization of the 7 groups of virus according to the Baltimore Classification
DNA viruses
Further information: DNA virus
Group I: viruses possess double-stranded DNA. Viruses that cause chickenpox and herpes are found here.
Group II: viruses possess single-stranded DNA.
Virus family Examples (common names) Virion
naked/enveloped Capsid
symmetry Nucleic acid type Group
1. Adenoviridae Adenovirus, infectious canine hepatitis virus Naked Icosahedral ds I
2. Papovaviridae Papillomavirus, polyomaviridae, simian vacuolating virus Naked Icosahedral ds circular I
3. Parvoviridae Parvovirus B19, canine parvovirus Naked Icosahedral ss II
4. Herpesviridae Herpes simplex virus, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus Enveloped Icosahedral ds I
5. Poxviridae Smallpox virus, cow pox virus, sheep pox virus, orf virus, monkey pox virus, vaccinia virus Complex coats Complex ds I
7. Anelloviridae Torque teno virus Naked Icosahedral ss circular II
7. Pleolipoviridae HHPV1, HRPV1, HGPV1, His2V Enveloped ss/ds linear/circular I/II
RNA viruses
Further information: RNA virus
Group III: viruses possess double-stranded RNA genomes, e.g. rotavirus.
Group IV: viruses possess positive-sense single-stranded RNA genomes. Many well known viruses are found in this group, including the picornaviruses (which is a family of viruses that includes well-known viruses like Hepatitis A virus, enteroviruses, rhinoviruses, poliovirus, and foot-and-mouth virus), SARS virus, hepatitis C virus, yellow fever virus, and rubella virus.
Group V: viruses possess negative-sense single-stranded RNA genomes. The deadly Ebola and Marburg viruses are well known members of this group, along with influenza virus, measles, mumps and rabies.
Virus Family Examples (common names) Capsid
naked/enveloped Capsid
Symmetry Nucleic acid type Group
1. Reoviridae Reovirus, rotavirus Naked Icosahedral ds III
2. Picornaviridae Enterovirus, rhinovirus, hepatovirus, cardiovirus, aphthovirus, poliovirus, parechovirus, erbovirus, kobuvirus, teschovirus, coxsackie Naked Icosahedral ss IV
3. Caliciviridae Norwalk virus Naked Icosahedral ss IV
4. Togaviridae Rubella virus, alphavirus Enveloped Icosahedral ss IV
5. Arenaviridae Lymphocytic choriomeningitis virus Enveloped Complex ss(−) V
6. Flaviviridae Dengue virus, hepatitis C virus, yellow fever virus, Zika virus Enveloped Icosahedral ss IV
7. Orthomyxoviridae Influenzavirus A, influenzavirus B, influenzavirus C, isavirus, thogotovirus Enveloped Helical ss(−) V
8. Paramyxoviridae Measles virus, mumps virus, respiratory syncytial virus, Rinderpest virus, canine distemper virus Enveloped Helical ss(−) V
9. Bunyaviridae California encephalitis virus, hantavirus Enveloped Helical ss(−) V
10. Rhabdoviridae Rabies virus Enveloped Helical ss(−) V
11. Filoviridae Ebola virus, Marburg virus Enveloped Helical ss(−) V
12. Coronaviridae Corona virus Enveloped Helical ss IV
13. Astroviridae Astrovirus Naked Icosahedral ss IV
14. Bornaviridae Borna disease virus Enveloped Helical ss(−) V
15. Arteriviridae Arterivirus, equine arteritis virus Enveloped Icosahedral ss IV
16. Hepeviridae Hepatitis E virus Naked Icosahedral ss IV
Reverse transcribing viruses
Group VI: viruses possess single-stranded RNA viruses that replicate through a DNA intermediate. The retroviruses are included in this group, of which HIV is a member.
Group VII: viruses possess double-stranded DNA genomes and replicate using reverse transcriptase. The hepatitis B virus can be found in this group.
Virus Family Examples (common names) Capsid
naked/enveloped Capsid
Symmetry Nucleic acid type Group
1. Retroviridae HIV Enveloped VI
2. Caulimoviridae Caulimovirus, Cacao swollen-shoot virus (CSSV) Naked VII
3. Hepadnaviridae Hepatitis B virus Enveloped Icosahedral circular, partially ds VII
Holmes classification
Holmes (1948) used Carl Linnaeus's system of binomial nomenclature to classify viruses into 3 groups under one order, Virales. They are placed as follows:

Group I: Phaginae (attacks bacteria)
Group II: Phytophaginae (attacks plants)
Group III: Zoophaginae (attacks animals)
LHT System of Virus Classification
The LHT System of Virus Classification is based on chemical and physical characters like nucleic acid (DNA or RNA), symmetry (helical or icosahedral or complex), presence of envelope, diameter of capsid, number of capsomers.[12] This classification was approved by the Provisional Committee on Nomenclature of Virus (PNVC) of the International Association of Microbiological Societies (1962).[citation needed] It is as follows:

Phylum Vira (divided into 2 subphyla)
Subphylum Deoxyvira (DNA viruses)
Class Deoxybinala (dual symmetry)
Order Urovirales
Family Phagoviridae
Class Deoxyhelica (helical symmetry)
Order Chitovirales
Family Poxviridae
Class Deoxycubica (cubical symmetry)
Order Peplovirales
Family Herpesviridae (162 capsomeres)
Order Haplovirales (no envelope)
Family Iridoviridae (812 capsomeres)
Family Adenoviridae (252 capsomeres)
Family Papiloviridae (72 capsomeres)
Family Paroviridae (32 capsomeres)
Family Microviridae (12 capsomeres)
Subphylum Ribovira (RNA viruses)
Class Ribocubica
Order Togovirales
Family Arboviridae
Order Tymovirales
Family Napoviridae
Family Reoviridae
Class Ribohelica
Order Sagovirales
Family Stomataviridae
Family Paramyxoviridae
Family Myxoviridae
Order Rhabdovirales
Suborder Flexiviridales
Family Mesoviridae
Family Peptoviridae
Suborder Rigidovirales
Family Pachyviridae
Family Protoviridae
Family Polichoviridae
Subviral agents
The following agents are smaller than viruses and have only some of their properties.

Viroids
Main article: Viroid
Family Avsunviroidae[13]
Genus Avsunviroid; type species: Avocado sunblotch viroid
Genus Pelamoviroid; type species: Peach latent mosaic viroid
Genus Elaviroid; type species: Eggplant latent viroid
Family Pospiviroidae[14]
Genus Pospiviroid; type species: Potato spindle tuber viroid
Genus Hostuviroid; type species: Hop stunt viroid
Genus Cocadviroid; type species: Coconut cadang-cadang viroid
Genus Apscaviroid; type species: Apple scar skin viroid
Genus Coleviroid; type species: Coleus blumei viroid 1
Satellites
Main article: Satellite (biology)
Satellites depend on co-infection of a host cell with a helper virus for productive multiplication. Their nucleic acids have substantially distinct nucleotide sequences from either their helper virus or host. When a satellite subviral agent encodes the coat protein in which it is encapsulated, it is then called a satellite virus.

Satellite viruses[15]
Single-stranded RNA satellite viruses
Subgroup 1: Chronic bee-paralysis satellite virus
Subgroup 2: Tobacco necrosis satellite virus
Double-stranded DNA satellite viruses (virophages)
Satellite nucleic acids
Single-stranded satellite DNAs
Double-stranded satellite RNAs
Single-stranded satellite RNAs
Subgroup 1: Large satellite RNAs
Subgroup 2: Small linear satellite RNAs
Subgroup 3: Circular satellite RNAs (virusoids)
Prions
Prions, named for their description as “proteinaceous and infectious particles”, lack any detectable (as of 2002) nucleic acids or virus-like particles. They resist inactivation procedures that normally affect nucleic acids.[16]

Mammalian prions:
Agents of spongiform encephalopathies
Fungal prions:
PSI+ prion of Saccharomyces cerevisiae
URE3 prion of Saccharomyces cerevisiae
RNQ/PIN+ prion of Saccharomyces cerevisiae
Het-s prion of Podospora anserina
Defective interfering particles
Main article: Defective interfering particle
Defective interfering RNA
Defective interfering DNA

 

Klasyfikacja wirusów – niniejsza klasyfikacja wirusów zwierzęcych jest oparta na systemie przyjętym przez Międzynarodowy Komitet Taksonomii Wirusów w roku 2000.

Systematyka wirusów jest oparta o zasady tzw. uniwersalny system taksonomii wirusów. Podstawowe jego cechy to:

Nazwy rzędów mają przyrostek -virales w nazwie łacińskiej. W obrębie rzędów grupuje się rodziny o podobnej charakterystyce, różne od pozostałych rodzin i rzędów. Założeniem jest grupowanie rodzin o udowodnionym pochodzeniu monofiletycznym.
Nazwy rodzin mają przyrostek -viridae w nazwie łacińskiej. Rodziny grupują rodzaje wirusów o współdzielonych właściwościach. Czasami rodziny są dzielone na podrodziny (przyrostek -virinae), co pozwala rozróżnić mniejsze grupy rodzajów.
Nazwy rodzajów kończą się przyrostkiem -virus i grupują gatunki o określonych, wspólnych cechach.
Gatunki wyróżnia się na podstawie kryteriów ekologicznych oraz sposobu replikacji.
Zalecenia dotyczące pisowni są następujące. Kursywą powinno wyróżniać się nazwy ustalone przez komitet, niezależnie od tego, czy są to nazwy łacińskie, czy angielskie. Z kolei nazwy nieprzyjęte oficjalnie, nawet jeśli występują w obiegu, powinny być pisane czcionką prostą. Dotyczy to wszystkich taksonów.

Poniżej podano taksonomię do rangi rodzaju. W przypadku wirusów o dużym znaczeniu, zwłaszcza medycznym, podano także nazwy gatunkowe.

Spis treści
1 Wirusy dsDNA – zawierają dwuniciowy DNA
2 Wirusy ssDNA – zawierają jednoniciowy DNA
3 Wirusy używające odwrotnej transkryptazy
4 Wirusy dsRNA – zawierają dwuniciowy RNA
5 Wirusy ssRNA(−) – zawierają jednoniciowy RNA o ujemnej polarności
6 Wirusy ssRNA(+) – zawierają RNA o dodatniej polarności
7 Systematyka według ICTV (2013)[1]
8 Przypisy
Wirusy dsDNA – zawierają dwuniciowy DNA
Rodzina: Ascoviridae
Rodzaj: Ascovirus
Rodzina: Asfarviridae
Rodzina: Baculoviridae (Bakulowirusy)
Rodzaj: Nucleopolyhedrovirus
Rodzaj: Granulovirus
Rodzina: Iridoviridae
Rodzaj: Iridovirus
Rodzaj: Chloriridovirus
Rodzaj: Ranavirus
Rodzaj: Lymphocystivirus
Rodzina: Herpesviridae (Herpeswirusy)
Podrodzina: Alphaherpesvirinae
Rodzaj: Simplexvirus (wirus opryszczki pospolitej)
Human herpesvirus 1 (HHV-1), ludzki herpeswirus typu 1, zwyczajowo Herpes simplex virus 1 (HSV-1) – wirus opryszczki pospolitej typu 1, herpeswirus typu 2
Human herpesvirus 2 (HHV-2), ludzki herpeswirus typu 2, zwyczajowo Herpes simplex virus 2 (HSV-2) – wirus opryszczki pospolitej typu 2, herpeswirus typu 2
Rodzaj: Varicellovirus
Human herpesvirus 3 (HHV-3), ludzki herpeswirus typu 3, zwyczajowo Varicella-zoster virus (VZV) – wirus ospy wietrznej-półpaśca
Rodzaj: „Marek's disease-like viruses”
Rodzaj: „ILTV-like viruses”
Podrodzina: Bethaherpesvirinae
Rodzaj: Cytomegalovirus
Human herpesvirus 5 (HHV-5), ludzki herpesvirus typu 5, zwyczajowo wirus cytomegalii, cytomegalowirus (CMV, HCMV)
Rodzaj: Muromegalovirus
Rodzaj: Roseolovirus
Human herpesvirus 6 (HHV-6), ludzki herpeswirus typu 6, zwyczajowo wirus rumienia nagłego typu 6
Human herpesvirus 7 (HHV-7), ludzki herpeswirus typu 7, zwyczajowo wirus rumienia nagłego typu 7
Podrodzina: Gammaherpesvirinae
Rodzaj: Lymphocryptovirus
Human herpesvirus 4 (HHV-4), ludzki herpesvirus typu 4, zwyczajowo wirus Epsteina-Barr (EBV)
Human herpesvirus 8 (HHV-8), ludzki herpesvirus typu 8
Rodzaj: Rhadinovirus
Rodzina: Adenoviridae (Adenowirusy)
Rodzaj: Mastadenovirus (Adenowirusy ssaków)
Human adenovirus A (HAdV-A), ludzki adenowirus A
Human adenovirus B (HAdV-B), ludzki adenowirus B
Human adenovirus C (HAdV-C), ludzki adenowirus C
Human adenovirus D (HAdV-D), ludzki adenowirus D
Human adenovirus E (HAdV-E), ludzki adenowirus E
Human adenovirus F (HAdV-F), ludzki adenowirus F
Rodzaj: Aviadenovirus (Adenowirusy ptaków)
Rodzina: Myoviridae (Fagi T-parzyste)
Rodzina: Siphoviridae (bakteriofag lambda)
Rodzina: Polyomaviridae (Poliomawirusy)
Rodzaj: Polyomavirus
Simian virus 40 (SV40)
BK polyomavirus (BKPyV), wirus BK
JC polyomavirus (JCPyV), wirus JC
Rodzina: Papillomaviridae (Papillomawirusy)
Rodzaj: Papillomavirus
Human papillomavirus, wirus brodawczaka ludzkiego
Rodzina: Poxviridae (Pokswirusy)
Podrodzina: Chordopoxvirinae
Rodzaj: Orthopoxvirus
Vaccinia virus (VACV), wirus krowianki
Variola virus (VARV), wirus ospy prawdziwej
Rodzaj: Parapoxvirus
Rodzaj: Avipoxvirus
Rodzaj: Capripoxvirus
Rodzaj: Leporipoxvirus
Rodzaj: Suipoxvirus
Rodzaj: Molluscipoxvirus
Molluscum contagiosum virus (MOCV), wirus mięczaka zakaźnego
Rodzaj: Yabapoxvirus
Podrodzina: Entomopoxvirinae
Rodzaj: Entomopoxvirus A
Rodzaj: Entomopoxvirus B
Rodzaj: Entomopoxvirus C
Rodzina: Polydnaviridae
Rodzaj: Ichnovirus
Rodzaj: Bracovirus
Wirusy ssDNA – zawierają jednoniciowy DNA
Rodzina: Circoviridae
Rodzaj: Circovirus
Rodzina: Parvoviridae (Parwowirusy)
Podrodzina: Parvovirinae
Rodzaj: Parvovirus
B19 virus (B19V), zwyczajowo parwowirus B19
Rodzaj: Erythrovirus
Rodzaj: Dependovirus
Podrodzina: Densovirinae
Rodzaj: Densovirus
Rodzaj: Iteravirus
Rodzaj: Brevidensovirus
Rodzina: Inoviridae (Inowirusy)
Rodzaj: Inovirus
Rodzaj: Plectrovirus
Rodzina: Microviridae (Mikrowirusy)
Wirusy używające odwrotnej transkryptazy
Rodzina: Hepadnaviridae (Hepadnawirusy)
Rodzaj: Orthohepadnavirus
Hepatitis B virus (HBV), wirus zapalenia wątroby typu B
Rodzaj: Avihepadnavirus
Rodzina: Retroviridae (Retrowirusy)
Rodzaj: Alpharetrovirus
Rodzaj: Betaretrovirus
Rodzaj: Gammaretrovirus
Rodzaj: Deltaretrovirus
Primate T-lymphotropic virus 1 (PTLV-1), zwyczajowo Human T-lymphotropic virus 1 (HTLV-1) – ludzki wirus T-limfotropowy typu 1
Primate T-lymphotropic virus 2 (PTLV-2), zwyczajowo Human T-lymphotropic virus 2 (HTLV-2) – ludzki wirus T-limfotropowy typu 2
Rodzaj: Epsilonretrovirus
Rodzaj: Lentivirus (Lentiwirusy)
Human immunodificiency virus 1 (HIV-1), ludzki wirus upośledzenia odporności typu 1
Human immunodificiency virus 2 (HIV-2), ludzki wirus upośledzenia odporności typu 2
Rodzaj: Spumavirus
Rodzina: Pseudoviridae
Rodzaj: Pseudovirus – tylko rośliny i drożdże, zapisany dla zachowania kompletności powyższej rodziny
Rodzaj: Hemivirus – zarówno bezkręgowce, jak i drożdże
Rodzina: Metaviridae
Rodzaj: Metavirus – rośliny i bezkręgowce
Rodzaj: Errantivirus
Wirusy dsRNA – zawierają dwuniciowy RNA
Rodzina: Reoviridae (Reowirusy)
Rodzaj Orthoreovirus
Rodzaj Orbivirus (Orbiwirusy)
Rodzaj Rotavirus (Rotawirusy)
Rotavirus A (RV-A)
Rotavirus B (RV-B)
Rodzaj Coltivirus
Colorado tick fever virus (CTFV), wirus gorączki kleszczowej Kolorado
Rodzaj Aquareovirus
Rodzaj Cypovirus
Rodzaj Fijivirus – wyłącznie roślinne
Rodzaj Phytoreovirus – wyłącznie roślinne
Rodzaj Oryzavirus – wyłącznie roślinne
Rodzina: Birnaviridae
Rodzaj: Aquabirnavirus
Rodzaj: Avibirnavirus
Rodzaj: Entomobirnavirus
Wirusy ssRNA(−) – zawierają jednoniciowy RNA o ujemnej polarności
Rodzina: Orthomyxoviridae (Ortomyksowirusy)
Rodzaj: Influenza A virus (FLUAV), zwyczajowo wirus grypy A
Rodzaj: Influenza B virus (FLUBV), zwyczajowo wirus grypy B
Rodzaj: Influenza C virus (FLUCV), zwyczajowo wirus grypy C
Rodzaj: Thogotovirus
Rząd: Mononegavirales
Rodzina: Paramyxoviridae (Paramyksowirusy)
Podrodzina: Paramyxovirinae
Rodzaj: Respirovirus
Human parainfluenza virus 1 (HPIV-1), zwyczajowo wirus paragrypy typu 1
Human parainfluenza virus 3 (HPIV-3), zwyczajowo wirus paragrypy typu 3
Rodzaj: Morbillivirus
Measles virus (MEV) – wirus odry
Rodzaj: Rubulavirus
Mumps virus (MuV), zwyczajowo wirus nagminnego zapalenia ślinianek przyusznych (wirus świnki)
Podrodzina: Pneumovirinae
Rodzaj: Pneumovirus
Human respiratory syncytial virus (HRSV), zwyczajowo ludzki syncytialny wirus oddechowy (wirus RSV)
Rodzaj: Metapneumovirus
Rodzina: Rhabdoviridae (Rabdowirusy)
Rodzaj: Vesiculovirus
Vesicular stomatitis New Jersey virus (VSNJV), zwyczajowo wirus pęcherzykowatego zapalenia jamy ustnej
Rodzaj: Lyssavirus
Rabies virus (RABV), zwyczajowo wirus wścieklizny
Rodzaj: Ephemerovirus
Rodzaj: Novirhabdovirus
Rodzaj: Cytorhabdovirus – wyłącznie roślinny
Rodzaj: Nucleorhabdovirus – wyłącznie roślinny
Rodzina: Bornaviridae (Bornawirusy)
Rodzaj: Bornavirus
Borna disease virus (BDV) – wirus choroby Borna
Rodzina: Filoviridae (Filowirusy)
Rodzaj: Ebola-like viruses
Zaire Ebola virus – wirus Ebola
Rodzaj: Marburg-like viruses
Marburg virus – wirus Marburg
Rodzina: Bunyaviridae (Buniawirusy)
Rodzaj: Bunyavirus
Rodzaj: Hantavirus Hantawirusy – pod tym hasłem znajduje się opis poniższych gatunków
Hantaan virus (HTNV), zwyczajowo wirus Hantaan, wirus Hanta, hantawirus
Dobrava-Belgrad virus (DOBV), zwyczajowo wirus Dobrawa-Belgrad
Puumala virus (PUUV), zwyczajowo wirus Puumala
Seoul virus (SEOV), zwyczajowo wirus Seoul
Sin Nombre virus (SNV), zwyczajowo wirus Sin Nombre
Rodzaj: Nairovirus
Rodzaj: Phlebovirus
Rift Valley fever virus (RVFV), zwyczajowo wirus gorączki Doliny Rift
Rodzaj: Tospovirus
Rodzina: Arenaviridae (Arenawirusy)
Rodzaj: Arenavirus
Lassa virus (LASV), zwyczajowo wirus gorączki Lassa
Arenavirusy Nowego Świata
Junin virus (JUNV), zwyczajowo wirus Junin
Machupo virus (MACV), zwyczajowo wirus Machupo
Guanarito virus (GTOV), zwyczajowo wirus Guanarito
Sabia virus (SABV), zwyczajowo wirus Sabia
Rodzaj: Deltavirus
Hepatitis delta virus (HDV), zwyczajowo wirus zapalenia wątroby typu D
Wirusy ssRNA(+) – zawierają RNA o dodatniej polarności
Rodzina: Picornaviridae (Pikornawirusy)
Rodzaj: Enterovirus
ludzkie enterowirusy (wirusy Coxsackie)
wirusy ECHO; echowirusy
Poliovirus, zwyczajowo wirus polio, poliowirus
Rodzaj: Rhinvirus (Rinowirusy)
Human rhinovirus A (HRV-A), zwyczajowo wirus przeziębienia typu A
Human rhinovirus B (HRV-B), zwyczajowo wirus przeziębienia typu B
Rodzaj: Hepatovirus
Hepatitis A virus (HAV), zwyczajowo wirus zapalenia wątroby typu A
Rodzaj: Cardiovirus
Rodzaj: Aphthovirus
Foot-and-mouth disease virus (FMDV) – wirus pryszczycy
Rodzaj: Parechovirus
Rodzina: Caliciviridae (Kaliciwirusy)
Rodzaj: Vesivirus
Rodzaj: Lagovirus
Rodzaj: Norwalk-like viruses
Norwalk virus (NV), zwyczajowo wirus Norwalk
Rodzaj: Sapporo-like viruses
Sapporo virus (SV), zwyczajowo wirus Sapporo
Rodzina: Astroviridae (Astrowirusy)
Rodzaj: Astrovirus
Human astrovirus (HastV), zwyczajowo ludzki astrowirus
Rodzina: Nodaviridae
Rodzaj: Alphanodavirus
Rodzaj: Betanodavirus
Rodzina: Tetraviridae
Rodzaj: Betatetravirus
Rodzaj: Omegatetravirus
Rząd: Nidovirales
Rodzina Coronaviridae (Koronawirusy)
Rodzaj: Coronavirus
Rodzaj: Torovirus
Rodzina: Togaviridae (Togawirusy)
Rodzaj: Alphavirus
Rodzaj: Rubivirus
Rubella virus (RUBV), zwyczajowo wirus różyczki
Rodzina: Flaviviridae (Flawiwirusy)
Rodzaj: Flavivirus
Tick-borne encephalitis virus (TBEV), zwyczajowo wirus kleszczowego zapalenia mózgu
Yellow fever virus (YFV), zwyczajowo wirus żółtej gorączki, wirus żółtej febry
Dengue virus (DENV), zwyczajowo wirus dengi
West Nile virus (WNV), zwyczajowo wirus gorączki Zachodniego Nilu
Rodzaj: Pestivirus
Rodzaj: Hepacivirus
Hepatitis C virus (HCV), zwyczajowo wirus zapalenia wątroby typu C
Rodzina: Arterivirdae
Rodzaj: Arterivirus
Systematyka według ICTV (2013)[1]
Rząd Caudovirales
Rodzina Myoviridae
Rodzina Podoviridae
Rodzina Siphoviridae
Rząd Herpesvirales
Rodzina Alloherpesviridae
Rodzina Herpesviridae
Rodzina Malacoherpesviridae
Rząd Ligamenvirales
Rodzina Lipothrixviridae
Rodzina Rudiviridae
Rząd Mononegavirales
Rodzina Bornaviridae
Rodzina Filoviridae
Rodzina Nyamiviridae
Rodzina Paramyxoviridae
Rodzina Rhabdoviridae
Rząd Nidovirales
Rodzina Arteriviridae
Rodzina Coronaviridae
Rodzina Mesoniviridae
Rodzina Roniviridae
Rząd Picornavirales
Rodzina Dicistroviridae
Rodzina Iflaviridae
Rodzina Marnaviridae
Rodzina Picornaviridae
Rodzina Secoviridae
2 rodzaje incertae sedis
Rząd Tymovirales
Rodzina Alphaflexiviridae
Rodzina Betaflexiviridae
Rodzina Gammaflexiviridae
Rodzina Tymoviridae
rodziny incertae sedis (77)
Rodzina Adenoviridae
Rodzina Alphatetraviridae
Rodzina Alvernaviridae
Rodzina Amalgaviridae
Rodzina Ampullaviridae
Rodzina Anelloviridae
Rodzina Arenaviridae
Rodzina Ascoviridae
Rodzina Asfarviridae
Rodzina Astroviridae
Rodzina Avsunviroidae
Rodzina Baculoviridae
Rodzina Barnaviridae
Rodzina Benyviridae
Rodzina Bicaudaviridae
Rodzina Bidnaviridae
Rodzina Birnaviridae
Rodzina Bromoviridae
Rodzina Bunyaviridae
Rodzina Caliciviridae
Rodzina Carmotetraviridae
Rodzina Caulimoviridae
Rodzina Chrysoviridae
Rodzina Circoviridae
Rodzina Clavaviridae
Rodzina Closteroviridae
Rodzina Corticoviridae
Rodzina Cystoviridae
Rodzina Endornaviridae
Rodzina Flaviviridae
Rodzina Fuselloviridae
Rodzina Geminiviridae
Rodzina Globuloviridae
Rodzina Guttaviridae
Rodzina Hepadnaviridae
Rodzina Hepeviridae
Rodzina Hypoviridae
Rodzina Hytrosaviridae
Rodzina Inoviridae
Rodzina Iridoviridae
Rodzina Leviviridae
Rodzina Luteoviridae
Rodzina Marseilleviridae
Rodzina Megabirnaviridae
Rodzina Metaviridae
Rodzina Microviridae
Rodzina Mimiviridae
Rodzina Nanoviridae
Rodzina Narnaviridae
Rodzina Nimaviridae
Rodzina Nodaviridae
Rodzina Nudiviridae
Rodzina Ophioviridae
Rodzina Orthomyxoviridae
Rodzina Papillomaviridae
Rodzina Partitiviridae
Rodzina Parvoviridae
Rodzina Permutotetraviridae
Rodzina Phycodnaviridae
Rodzina Picobirnaviridae
Rodzina Plasmaviridae
Rodzina Polydnaviridae
Rodzina Polyomaviridae
Rodzina Pospiviroidae
Rodzina Potyviridae
Rodzina Poxviridae
Rodzina Pseudoviridae
Rodzina Quadriviridae
Rodzina Reoviridae
Rodzina Retroviridae
Rodzina Spiraviridae
Rodzina Tectiviridae
Rodzina Togaviridae
Rodzina Tombusviridae
Rodzina Totiviridae
Rodzina Turriviridae
Rodzina Virgaviridae
rodzaje incertae sedis (15)

 

A plasmid is a small DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; however, plasmids are sometimes present in archaea and eukaryotic organisms. In nature, plasmids often carry genes that benefit the survival of the organism, such as by providing antibiotic resistance. While the chromosomes are big and contain all the essential genetic information for living under normal conditions, plasmids usually are very small and contain only additional genes that may be useful in certain situations or conditions. Artificial plasmids are widely used as vectors in molecular cloning, serving to drive the replication of recombinant DNA sequences within host organisms. In the laboratory, plasmids may be introduced into a cell via transformation.

Plasmids are considered replicons, units of DNA capable of replicating autonomously within a suitable host. However, plasmids, like viruses, are not generally classified as life.[1] Plasmids are transmitted from one bacterium to another (even of another species) mostly through conjugation.[2] This host-to-host transfer of genetic material is one mechanism of horizontal gene transfer, and plasmids are considered part of the mobilome. Unlike viruses, which encase their genetic material in a protective protein coat called a capsid, plasmids are “naked” DNA and do not encode genes necessary to encase the genetic material for transfer to a new host. However, some classes of plasmids encode the conjugative “sex” pilus necessary for their own transfer. The size of the plasmid varies from 1 to over 200 kbp,[3] and the number of identical plasmids in a single cell can range anywhere from one to thousands under some circumstances.

Contents
1 History
2 Properties and characteristics
3 Classifications and types
4 Vectors
4.1 Cloning
4.2 Protein production
4.3 Gene therapy
4.4 Disease models
5 Episomes
6 Plasmid maintenance
7 Yeast plasmids
8 Plasmid DNA extraction
9 Conformations
10 Software for bioinformatics and design
11 Plasmid collections
12 See also
13 References
14 Further reading
14.1 Episomes
15 External links
History
The term plasmid was introduced in 1952 by the American molecular biologist Joshua Lederberg to refer to “any extrachromosomal hereditary determinant.”[4] The term's early usage included any bacterial genetic material that exists extrachromosomally for at least part of its replication cycle, but because that description includes bacterial viruses, the notion of plasmid was refined over time to comprise genetic elements that reproduce autonomously.[5] Later in 1968, it was decided that the term plasmid should be adopted as the term for extrachromosomal genetic element,[6] and to distinguish it from viruses, the definition was narrowed to genetic elements that exist exclusively or predominantly outside of the chromosome and can replicate autonomously.[5]

Properties and characteristics

There are two types of plasmid integration into a host bacteria: Non-integrating plasmids replicate as with the top instance, whereas episomes, the lower example, can integrate into the host chromosome.
In order for plasmids to replicate independently within a cell, they must possess a stretch of DNA that can act as an origin of replication. The self-replicating unit, in this case the plasmid, is called a replicon. A typical bacterial replicon may consist of a number of elements, such as the gene for plasmid-specific replication initiation protein (Rep), repeating units called iterons, DnaA boxes, and an adjacent AT-rich region.[5] Smaller plasmids make use of the host replicative enzymes to make copies of themselves, while larger plasmids may carry genes specific for the replication of those plasmids. A few types of plasmids can also insert into the host chromosome, and these integrative plasmids are sometimes referred to as episomes in prokaryotes.[7]

Plasmids almost always carry at least one gene. Many of the genes carried by a plasmid are beneficial for the host cells, for example: enabling the host cell to survive in an environment that would otherwise be lethal or restrictive for growth. Some of these genes encode traits for antibiotic resistance or resistance to heavy metal, while others may produce virulence factors that enable a bacterium to colonize a host and overcome its defences, or have specific metabolic functions that allow the bacterium to utilize a particular nutrient, including the ability to degrade recalcitrant or toxic organic compounds.[5] Plasmids can also provide bacteria with the ability to fix nitrogen. Some plasmids, however, have no observable effect on the phenotype of the host cell or its benefit to the host cells cannot be determined, and these plasmids are called cryptic plasmids.[8]

Naturally occurring plasmids vary greatly in their physical properties. Their size can range from very small mini-plasmids of less than a 1 kilobase pairs (Kbp), to very large megaplasmids of several megabase pairs (Mbp). At the upper end, little can differentiate between a megaplasmid and a minichromosome. Plasmids are generally circular, but examples of linear plasmids are also known. These linear plasmids require specialized mechanisms to replicate their ends.[5]

Plasmids may be present in an individual cell in varying number, ranging from one to several hundreds. The normal number of copies of plasmid that may be found in a single cell is called the Plasmid copy number, and is determined by how the replication initiation is regulated and the size of the molecule. Larger plasmids tend to have lower copy numbers.[7] Low-copy-number plasmids that exist only as one or a few copies in each bacterium are, upon cell division, in danger of being lost in one of the segregating bacteria. Such single-copy plasmids have systems that attempt to actively distribute a copy to both daughter cells. These systems, which include the parABS system and parMRC system, are often referred to as the partition system or partition function of a plasmid.

Classifications and types

Overview of bacterial conjugation

Electron micrograph of a DNA fiber bundle, presumably of a single bacterial chromosome loop

Electron micrograph of a bacterial DNA plasmid (chromosome fragment)
Plasmids may be classified in a number of ways. Plasmids can be broadly classified into conjugative plasmids and non-conjugative plasmids. Conjugative plasmids contain a set of transfer or tra genes which promote sexual conjugation between different cells.[7] In the complex process of conjugation, plasmid may be transferred from one bacterium to another via sex pili encoded by some of the tra genes (see figure).[9] Non-conjugative plasmids are incapable of initiating conjugation, hence they can be transferred only with the assistance of conjugative plasmids. An intermediate class of plasmids are mobilizable, and carry only a subset of the genes required for transfer. They can parasitize a conjugative plasmid, transferring at high frequency only in its presence.

Plasmids can also be classified into incompatibility groups. A microbe can harbour different types of plasmids, but different plasmids can only exist in a single bacterial cell if they are compatible. If two plasmids are not compatible, one or the other will be rapidly lost from the cell. Different plasmids may therefore be assigned to different incompatibility groups depending on whether they can coexist together. Incompatible plasmids (belonging to the same incompatibility group) normally share the same replication or partition mechanisms and can thus not be kept together in a single cell.[10][11]

Another way to classify plasmids is by function. There are five main classes:

Fertility F-plasmids, which contain tra genes. They are capable of conjugation and result in the expression of sex pili.
Resistance (R) plasmids, which contain genes that provide resistance against antibiotics or poisons. Historically known as R-factors, before the nature of plasmids was understood.
Col plasmids, which contain genes that code for bacteriocins, proteins that can kill other bacteria.
Degradative plasmids, which enable the digestion of unusual substances, e.g. toluene and salicylic acid.
Virulence plasmids, which turn the bacterium into a pathogen.
Plasmids can belong to more than one of these functional groups.

Vectors
Further information: Vector (molecular biology)
Artificially constructed plasmids may be used as vectors in genetic engineering. These plasmids serve as important tools in genetics and biotechnology labs, where they are commonly used to clone and amplify (make many copies of) or express particular genes.[12] A wide variety of plasmids are commercially available for such uses. The gene to be replicated is normally inserted into a plasmid that typically contains a number of features for their use. These include a gene that confers resistance to particular antibiotics (ampicillin is most frequently used for bacterial strains), an origin of replication to allow the bacterial cells to replicate the plasmid DNA, and a suitable site for cloning (referred to as a multiple cloning site).

DNA structural instability can be defined as a series of spontaneous events that culminate in an unforeseen rearrangement, loss, or gain of genetic material. Such events are frequently triggered by the transposition of mobile elements or by the presence of unstable elements such as non-canonical (non-B) structures. Accessory regions pertaining to the bacterial backbone may engage in a wide range of structural instability phenomena. Well-known catalysts of genetic instability include direct, inverted, and tandem repeats, which are known to be conspicuous in a large number of commercially available cloning and expression vectors.[13] Insertion sequences can also severely impact plasmid function and yield, by leading to deletions and rearrangements, activation, down-regulation or inactivation of neighboring gene expression.[14] Therefore, the reduction or complete elimination of extraneous noncoding backbone sequences would pointedly reduce the propensity for such events to take place, and consequently, the overall recombinogenic potential of the plasmid.[15][16]

A schematic representation of the pBR322 plasmid, one of the first plasmids to be used widely as a cloning vector. Shown on the plasmid diagram are the genes encoded (amp and tet for ampicillin and tetracycline resistance respectively), its origin of replication (ori), and various restriction sites (indicated in blue).
Cloning
Main article: Cloning vector
Plasmids are the most-commonly used bacterial cloning vectors.[17] These cloning vectors contain a site that allows DNA fragments to be inserted, for example a multiple cloning site or polylinker which has several commonly used restriction sites to which DNA fragments may be ligated. After the gene of interest is inserted, the plasmids are introduced into bacteria by a process called transformation. These plasmids contain a selectable marker, usually an antibiotic resistance gene, which confers on the bacteria an ability to survive and proliferate in a selective growth medium containing the particular antibiotics. The cells after transformation are exposed to the selective media, and only cells containing the plasmid may survive. In this way, the antibiotics act as a filter to select only the bacteria containing the plasmid DNA. The vector may also contain other marker genes or reporter genes to facilitate selection of plasmid with cloned insert. Bacteria containing the plasmid can then be grown in large amounts, harvested, and the plasmid of interest may then be isolated using various methods of plasmid preparation.

A plasmid cloning vector is typically used to clone DNA fragments of up to 15 kbp.[18] To clone longer lengths of DNA, lambda phage with lysogeny genes deleted, cosmids, bacterial artificial chromosomes, or yeast artificial chromosomes are used.

Protein production
Main article: Expression vector
Another major use of plasmids is to make large amounts of proteins. In this case, researchers grow bacteria containing a plasmid harboring the gene of interest. Just as the bacterium produces proteins to confer its antibiotic resistance, it can also be induced to produce large amounts of proteins from the inserted gene. This is a cheap and easy way of mass-producing the protein the gene codes for, for example, insulin.

Gene therapy
Main article: Vectors in gene therapy
Plasmid may also be used for gene transfer into human cells as potential treatment in gene therapy so that it may express the protein that is lacking in the cells. Some strategies of gene therapy require the insertion of therapeutic genes at pre-selected chromosomal target sites within the human genome. Plasmid vectors are one of many approaches that could be used for this purpose. Zinc finger nucleases (ZFNs) offer a way to cause a site-specific double-strand break to the DNA genome and cause homologous recombination. Plasmids encoding ZFN could help deliver a therapeutic gene to a specific site so that cell damage, cancer-causing mutations, or an immune response is avoided.[19]

Disease models
Plasmids were historically used to genetically engineer the embryonic stem cells of rats to create rat genetic disease models. The limited efficiency of plasmid-based techniques precluded their use in the creation of more accurate human cell models. However, developments in Adeno-associated virus recombination techniques, and Zinc finger nucleases, have enabled the creation of a new generation of isogenic human disease models.

Episomes
“Episome” redirects here. For the album by Bill Laswell, Otomo Yoshihide and Tatsuya Yoshida, see Episome (album).
The term episome was introduced by François Jacob and Élie Wollman in 1958 to refer to extra-chromosomal genetic material that may replicate autonomously or become integrated into the chromosome.[20][21] Since the term was introduced, however, its use has shifted, as plasmid has become the preferred term for autonomously replicating extrachromosomal DNA. At a 1968 symposium in London some participants suggested that the term episome be abandoned, although others continued to use the term with a shift in meaning.[22][23]

Today some authors use episome in the context of prokaryotes to refer to a plasmid that is capable of integrating into the chromosome. The integrative plasmids may be replicated and stably maintained in a cell through multiple generations, but always at some stage they exist as an independent plasmid molecule.[24] In the context of eukaryotes, the term episomes is used to mean a non-integrated extrachromosomal closed circular DNA molecule that may be replicated in the nucleus.[25][26] Viruses are the most common examples of this, such as herpesviruses, adenoviruses, and polyomaviruses, but some are plasmids. Other examples include aberrant chromosomal fragments, such as double minute chromosomes, that can arise during artificial gene amplifications or in pathologic processes (e.g., cancer cell transformation). Episomes in eukaryotes behave similarly to plasmids in prokaryotes in that the DNA is stably maintained and replicated with the host cell. Cytoplasmic viral episomes (as in poxvirus infections) can also occur. Some episomes, such as herpesviruses, replicate in a rolling circle mechanism, similar to bacterial phage viruses. Others replicate through a bidirectional replication mechanism (Theta type plasmids). In either case, episomes remain physically separate from host cell chromosomes. Several cancer viruses, including Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus, are maintained as latent, chromosomally distinct episomes in cancer cells, where the viruses express oncogenes that promote cancer cell proliferation. In cancers, these episomes passively replicate together with host chromosomes when the cell divides. When these viral episomes initiate lytic replication to generate multiple virus particles, they in general activate cellular innate immunity defense mechanisms that kill the host cell.

Plasmid maintenance
Main article: Addiction module
Some plasmids or microbial hosts include an addiction system or postsegregational killing system (PSK), such as the hok/sok (host killing/suppressor of killing) system of plasmid R1 in Escherichia coli.[27] This variant produces both a long-lived poison and a short-lived antidote. Several types of plasmid addiction systems (toxin/ antitoxin, metabolism-based, ORT systems) were described in the literature[28] and used in biotechnical (fermentation) or biomedical (vaccine therapy) applications. Daughter cells that retain a copy of the plasmid survive, while a daughter cell that fails to inherit the plasmid dies or suffers a reduced growth-rate because of the lingering poison from the parent cell. Finally, the overall productivity could be enhanced.

In contrast, virtually all biotechnologically used plasmids (such as pUC18, pBR322 and derived vectors) do not contain toxin-antitoxin addiction systems and thus need to be kept under antibiotic pressure to avoid plasmid loss.

Yeast plasmids
Yeasts naturally harbour various plasmids. Notable among them are 2 μm plasmids – small circular plasmids often used for genetic engineering of yeast – and linear pGKL plasmids from Kluyveromyces lactis, that are responsible for killer phenotypes.[29]

Other types of plasmids are often related to yeast cloning vectors that include:

Yeast integrative plasmid (YIp), yeast vectors that rely on integration into the host chromosome for survival and replication, and are usually used when studying the functionality of a solo gene or when the gene is toxic. Also connected with the gene URA3, that codes an enzyme related to the biosynthesis of pyrimidine nucleotides (T, C);
Yeast Replicative Plasmid (YRp), which transport a sequence of chromosomal DNA that includes an origin of replication. These plasmids are less stable, as they can get lost during the budding.
Plasmid DNA extraction
As alluded to above, plasmids are often used to purify a specific sequence, since they can easily be purified away from the rest of the genome. For their use as vectors, and for molecular cloning, plasmids often need to be isolated.

There are several methods to isolate plasmid DNA from bacteria, the archetypes of which are the miniprep and the maxiprep/bulkprep.[12] The former can be used to quickly find out whether the plasmid is correct in any of several bacterial clones. The yield is a small amount of impure plasmid DNA, which is sufficient for analysis by restriction digest and for some cloning techniques.

In the latter, much larger volumes of bacterial suspension are grown from which a maxi-prep can be performed. In essence, this is a scaled-up miniprep followed by additional purification. This results in relatively large amounts (several hundreds micrograms) of very pure plasmid DNA.

In recent times, many commercial kits have been created to perform plasmid extraction at various scales, purity, and levels of automation. Commercial services can prepare plasmid DNA at quoted prices below $300/mg in milligram quantities and $15/mg in gram quantities (early 2007).

Conformations
Plasmid DNA may appear in one of five conformations, which (for a given size) run at different speeds in a gel during electrophoresis. The conformations are listed below in order of electrophoretic mobility (speed for a given applied voltage) from slowest to fastest:

Nicked open-circular DNA has one strand cut.
Relaxed circular DNA is fully intact with both strands uncut, but has been enzymatically relaxed (supercoils removed). This can be modeled by letting a twisted extension cord unwind and relax and then plugging it into itself.
Linear DNA has free ends, either because both strands have been cut or because the DNA was linear in vivo. This can be modeled with an electrical extension cord that is not plugged into itself.
Supercoiled (or covalently closed-circular) DNA is fully intact with both strands uncut, and with an integral twist, resulting in a compact form. This can be modeled by twisting an extension cord and then plugging it into itself.
Supercoiled denatured DNA is like supercoiled DNA, but has unpaired regions that make it slightly less compact; this can result from excessive alkalinity during plasmid preparation.
The rate of migration for small linear fragments is directly proportional to the voltage applied at low voltages. At higher voltages, larger fragments migrate at continuously increasing yet different rates. Thus, the resolution of a gel decreases with increased voltage.

At a specified, low voltage, the migration rate of small linear DNA fragments is a function of their length. Large linear fragments (over 20 kb or so) migrate at a certain fixed rate regardless of length. This is because the molecules 'resperate', with the bulk of the molecule following the leading end through the gel matrix. Restriction digests are frequently used to analyse purified plasmids. These enzymes specifically break the DNA at certain short sequences. The resulting linear fragments form 'bands' after gel electrophoresis. It is possible to purify certain fragments by cutting the bands out of the gel and dissolving the gel to release the DNA fragments.

Because of its tight conformation, supercoiled DNA migrates faster through a gel than linear or open-circular DNA.

Software for bioinformatics and design
The use of plasmids as a technique in molecular biology is supported by bioinformatics software. These programs record the DNA sequence of plasmid vectors, help to predict cut sites of restriction enzymes, and to plan manipulations. Examples of software packages that handle plasmid maps are ApE, Clone Manager, GeneConstructionKit, Geneious, Genome Compiler, LabGenius, Lasergene, MacVector, pDraw32, Serial Cloner, VectorFriends, Vector NTI, and WebDSV. These software help conduct entire experiments in silico before doing wet experiments.[30]

Plasmid collections
Many plasmids have been created over the years and researchers have given out plasmids to plasmid databases such as the non-profit organisations Addgene and BCCM/LMBP. One can find and request plasmids from those databases for research. Researcher also often upload plasmid sequences to the NCBI database, from which sequences of specific plasmids can be retrieved.

See also
Bacterial artificial chromosome
Bacteriophage
Provirus
Segrosome
Transposon
Triparental mating
Plasmidome
DNA recombination

 

Plazmid – cząsteczka pozachromosomowego DNA występująca w cytoplazmie komórki, zdolna do autonomicznej replikacji. Termin „plazmid” został po raz pierwszy zaproponowany przez Joshuę Lederberga w 1952 roku, jako genetyczna nazwa wszystkich znanych (w tamtym czasie) „pozachromosomowych cząstek genetycznych”, a w praktyce zaczął funkcjonować osiem lat później. Plazmidy występują przede wszystkim u prokariontów, ale znane są również plazmidy u eukariontów. Zazwyczaj plazmidy nie niosą genów metabolizmu podstawowego, a więc nie są komórce niezbędne do przeżycia. Mogą jednak kodować produkty potrzebne w pewnych specyficznych warunkach, na przykład geny oporności na antybiotyki lub umożliwiające rozkład i asymilację różnych związków odżywczych. Plazmidy mogą być przekazywane pomiędzy komórkami bakteryjnymi w czasie podziału komórki lub poprzez poziomy transfer genów, na przykład w procesie koniugacji, transdukcji i transformacji[1]. Uważa się, że plazmidy razem z wirionami pochodzą od wspólnego replikonu[2].

Spis treści
1 Budowa
2 Mobilność
3 Utrzymanie w komórce
3.1 Duża liczba kopii plazmidu
3.2 Systemy miejscowo specyficznej rekombinacji
3.3 Systemy partycyjne (aktywnego rozdziału)
3.4 Systemy addykcyjne
3.4.1 System cddAB
3.4.2 System hok-sok
4 Zastosowanie
5 Zobacz też
6 Przypisy
7 Bibliografia
8 Linki zewnętrzne
Budowa
Większość znanych plazmidów to niewielkie, kowalencyjnie zamknięte cząsteczki DNA. Najmniejsze plazmidy mogą mieć rozmiar około 1 kpz, największe zaś około 2000 kpz. Znane są również plazmidy naturalnie występujące w formie liniowej[3].

Plazmidy mogą kodować wiele genów związanych ze swoim utrzymaniem, replikacją oraz transferem do innych komórek. Replikacja plazmidu, niezależna od replikacji DNA chromosomowego, możliwa jest dzięki obecności miejsca ori (od ang. origin of replication), czyli sekwencji, w której następuje rozpoczęcie replikacji DNA[4].

Mobilność
Plazmidy mogą być przekazywane nie tylko z komórki macierzystej do komórek potomnych, ale także pomiędzy dwiema komórkami bakteryjnymi w procesie koniugacji. Obok transdukcji, transformacji i transfekcji koniugacja jest jednym z rodzajów poziomego transferu genów. Jest on istotny dla ewolucji bakterii, ponieważ umożliwia szybką adaptację do zmieniających się warunków środowiska. Ma to także znaczenie dla człowieka, gdyż większość genów oporności na antybiotyki kodowanych jest na plazmidach, co umożliwia przekazywanie oporności wśród bakterii chorobotwórczych, w tym należących do innych gatunków[5].

Utrzymanie w komórce
Jak zostało wspomniane, plazmidy zazwyczaj nie kodują żadnych informacji genetycznych niezbędnych dla przeżycia komórki. Do właściwości utrzymujących plazmidy w komórce należą[6]:

duża liczba kopii plazmidu
systemy miejscowo specyficznej rekombinacji (rozdziału multimerów) – mrs.
systemy partycyjne (aktywnego rozdziału) – par.
systemy addykcyjne, na przykład ccd.
Duża liczba kopii plazmidu
Niewielkie plazmidy występują zazwyczaj w komórce w wysokiej (od kilkunastu do kilkudziesięciu) liczbie kopii. Dzięki temu przy podziale komórki zapewnione jest bardzo wysokie prawdopodobieństwo odziedziczenia plazmidu przez komórki potomne. Im więcej kopii plazmidu, tym większe prawdopodobieństwo, że w wyniku podziału komórki nie powstanie komórka bezplazmidowa[6].

Systemy miejscowo specyficznej rekombinacji
Gdy w komórce znajduje się więcej niż jedna kopia plazmidu, spontanicznie zachodzi ich łączenie się poprzez sekwencje homologiczne, co powoduje powstawanie dimerów i oligomerów. Przy podziale komórki oligomery tworzą razem jedną cząsteczkę, która zostaje przekazana jednej z komórek potomnych. Zachodzi więc niebezpieczeństwo, że wszystkie plazmidy połączone w jedną cząsteczkę zostaną przekazane tylko jednej komórce, a druga komórka będzie pozbawiona plazmidu. Spowodowałoby to po pewnym czasie zwiększenie się w populacji liczby bakterii nie posiadających plazmidu[6].

Aby temu zapobiec, na plazmidzie mogą znajdować się geny systemu miejscowo specyficznej rekombinacji. Zawierają one specjalne sekwencje res oraz kodują białko resolwazę (rekombinazę). Resolwaza działa na sekwencje res i w drodze rekombinacji homologicznej powoduje rozdzielenie multimeru na pojedyncze plazmidy. Tego rodzaju system nie zapobiega jednak ponownemu tworzeniu multimerów, lecz jedynie rozdziela już istniejące[6].

Systemy partycyjne (aktywnego rozdziału)
Dzięki obecności tych systemów następuje aktywny i ściśle kontrolowany rozdział plazmidów do komórek potomnych. W skład systemów tego typu wchodzą specyficzne sekwencje DNA, wykazujące podobieństwo do eukariotycznych centromerów, oraz białka uczestniczące w procesie rozdziału. Podczas podziału komórki sekwencje centromeropodobne wiązane są przez rozpoznające je białka, do tych zaś przyłączają się kolejne białka bezpośrednio uczestniczące w rozdziale. Plazmidy zostają ustawione w płaszczyźnie równikowej, a następnie rozchodzą się do przeciwległych biegunów komórki[6].

Systemy addykcyjne

Ilustracja działania systemu addykcyjnego cddAB (objaśnienia w tekście)
Systemy addykcyjne powodują eliminację komórek, które nie odziedziczyły plazmidu podczas podziału komórki. Składają się na nie geny kodujące trwałą toksynę (truciznę) oraz labilną antytoksynę (antidotum). W komórce posiadającej plazmid zachodzi ekspresja obydwu tych genów, jednak antytoksyna znosi efekt działania toksyny. Po podziale komórki potomne dziedziczą po komórce macierzystej zarówno truciznę, jak i antidotum obecne w cytoplazmie. Jeśli komórka nie otrzymała przy podziale plazmidu, labilne antidotum jest szybko rozkładane, natomiast trwała trucizna jest dalej obecna w cytoplazmie i, w zależności od typu, powoduje efekt bakteriobójczy lub bakteriostatyczny. Jeśli natomiast komórka odziedziczyła plazmid, jest w stanie produkować własne antidotum[6].

Istnieją dwa typy systemów addykcyjnych:

Trucizna to białko, a antidotum to antysensowy RNA, uniemożliwiający translację mRNA trucizny.
Trucizna i antidotum to dwa białka, które razem tworzą nieaktywny kompleks.
System cddAB
Przykładem systemu addykcyjnego typu białko-białko jest system cddAB (patrz rysunek).

a) System tworzą dwa geny: cddA (2), kodujący antidotum (3), oraz cddB, (4) kodujący truciznę (5). Obydwa geny są transkrybowane ze wspólnego promotora (1), a więc tworzą operon.
b) Podczas normalnego funkcjonowania komórki bakteryjnej posiadającej plazmid kodujący system cddAB, trucizna pozostaje związana przez antidotum (6) i nie wywiera toksycznego wpływu na swój cel komórkowy (7), jakim w tym wypadku jest gyraza DNA.
(c) Jeśli komórka utraci plazmid z genami systemu cddAB, nietrwałe antidotum zostaje zdegradowane (8), a toksyna wiąże się ze swoim celem (9) hamując dalsze podziały komórki.
System hok-sok
Przykładem systemu addykcyjnego typu białko-RNA jest system hok/sok[6].

Zastosowanie
Plazmidy bakteryjne znalazły zastosowanie w inżynierii genetycznej jako wektory. Obecnie używa się plazmidów rekombinowanych, zawierających elementy wielu plazmidów naturalnych jednocześnie[7].

Zobacz też
wektor plazmidowy

 

Nanobacterium (/ˌnænoʊbækˈtɪəriəm/ NAN-oh-bak-TEER-ee-əm, pl. nanobacteria /ˌnænoʊbækˈtɪəriə/ NAN-oh-bak-TEER-ee-ə) is the unit or member name of a former proposed class of living organisms, specifically cell-walled microorganisms, now discredited, with a size much smaller than the generally accepted lower limit for life (about 200 nm for bacteria, like mycoplasma). Originally based on observed nano-scale structures in geological formations (including one meteorite), the status of nanobacteria was controversial, with some researchers suggesting they are a new class of living organism[1][2] capable of incorporating radiolabeled uridine,[3] and others attributing to them a simpler, abiotic nature.[4][5] One skeptic dubbed them “the cold fusion of microbiology”, in reference to a notorious episode of supposed erroneous science.[6] The term “calcifying nanoparticles” (CNPs) has also been used as a conservative name regarding their possible status as a life form.

Research tends to agree that these structures exist, and appear to replicate in some way.[7] However, the idea that they are living entities has now largely been discarded, and the particles are instead thought to be nonliving crystallizations of minerals and organic molecules.[8]

Contents
1 1981–2000
2 2001–present
3 See also
4 References
5 External links
1981–2000
In 1981 Torella and Morita described very small cells called ultramicrobacteria. Defined as being smaller than 300 nm, by 1982 MacDonell and Hood found that some could pass through a 200 nm membrane. Early in 1989, geologist Robert L. Folk found what he later identified as nannobacteria (written with double “n”), that is, nanoparticles isolated from geological specimens[9] in travertine from hot springs of Viterbo, Italy. Initially searching for a bacterial cause for travertine deposition, scanning electron microscope examination of the mineral where no bacteria were detectable revealed extremely small objects which appeared to be biological. His first oral presentation elicited what he called “mostly a stony silence”, at the 1992 Geological Society of America's annual convention.[10] He proposed that nanobacteria are the principal agents of precipitation of all minerals and crystals on Earth formed in liquid water, that they also cause all oxidation of metals, and that they are abundant in many biological specimens.[10]

In 1996, NASA scientist David McKay published a study suggesting the existence of nanofossils – fossils of Martian nanobacteria – in ALH84001, a meteorite originating from Mars and found in Antarctica.[11]

Nanobacterium sanguineum was proposed in 1998 as an explanation of certain kinds of pathologic calcification (apatite in kidney stones) by Finnish researcher Olavi Kajander and Turkish researcher Neva Ciftcioglu, working at the University of Kuopio in Finland. According to the researchers the particles self-replicated in microbiological culture, and the researchers further reported having identified DNA in these structures by staining.[12]

A paper published in 2000 by a team led by an NIH scientist John Cisar further tested these ideas. It stated that what had previously been described as “self-replication” was a form of crystalline growth. The only DNA detected in his specimens was identified as coming from the bacteria Phyllobacterium myrsinacearum, which is a common contaminant in PCR reactions.[4]

2001–present
In 2004 a Mayo Clinic team led by Franklin Cockerill, John Lieske, and Virginia M. Miller, reported to have isolated nanobacteria from diseased human arteries and kidney stones. Their results were published in 2004 and 2006 respectively.[3][13] Similar findings were obtained in 2005 by László Puskás at the DNA Lab, University of Szeged, Hungary. Dr. Puskás identified these particles in cultures obtained from human atherosclerotic aortic walls and blood samples of atherosclerotic patients but the group was unable to detect DNA in these samples.[14]

In 2005, Ciftcioglu and her research team at NASA used a rotating cell culture flask, which simulates some aspects of low-gravity conditions, to culture nanobacteria suspected of rapidly forming kidney stones in astronauts. In this environment, they were found to multiply five times faster than in normal Earth gravity. The study concluded that nanobacteria might have a potential role in forming kidney stones and may need to be screened for in crews pre-flight.[15]

The February 2008 Public Library of Science Pathogens (PLOS Pathogens) article focused on the comprehensive characterization of nanobacteria. The authors say that their results rule out the existence of nanobacteria as living entities and that they are instead a unique self-propagating entity, namely self-propagating mineral-fetuin complexes.[16]

An April 2008 Proceedings of the National Academy of Sciences (PNAS) article also reported that blood nanobacteria are not living organisms and stated that “CaCO3 precipitates prepared in vitro are remarkably similar to purported nanobacteria in terms of their uniformly sized, membrane-delineated vesicular shapes, with cellular division-like formations and aggregations in the form of colonies.”[5] The growth of such “biomorphic” inorganic precipitates was studied in detail in a 2009 Science paper, which showed that unusual crystal growth mechanisms can produce witherite precipitates from barium chloride and silica solutions that closely resemble primitive organisms.[17] The authors commented on the close resemblance of these crystals to putative nanobacteria, stating that their results showed that evidence for life cannot rest on morphology alone.

Further work on the importance of nanobacteria in geology by R. L. Folk and co-workers includes study of calcium carbonate Bahama ooids,[18] silicate clay minerals,[19] metal sulfides,[20] and iron oxides.[21] In all these chemically diverse minerals, the putative nanobacteria are approximately the same size, mainly 0.05 to 0.2 μm. This suggests a commonality of origin. At least for the type locality at Viterbo, Italy, the biogenicity of these minute cells has been supported by transmission electron microscopy (TEM).[22] Slices through a green bioslime showed entities from 0.4 down to as small as 0.09 μm with definite cell walls and interior dots resembling ribosomes; and even smaller objects with cell walls and lucent interiors with diameters of 0.05 μm.[23] Culturable organisms on earth are the same 0.05 μm size as the supposed nanobacteria on Mars.[24]

See also
Mycoplasma – smallest known bacteria (300 nm)
Nanoarchaeum – smallest known archaeum (400 nm)
Nanobe – possible smallest lifeforms (20 nm)
Pandoravirus – one of the largest known viruses (1000 nm)
Parvovirus – smallest known viruses (18–28 nm)
Pithovirus – largest known virus (1500 nm)
Prion – smallest known infectious agent (≈10 nm)
Protocell
Ultramicrobacteria – possible dormant forms of larger cells (200 nm)

 

Ultramicrobacteria are bacteria that are smaller than 0.1 μm3 under all growth conditions.[1][2][3] This term was coined in 1981, describing cocci in seawater that were less than 0.3 μm in diameter.[4] Ultramicrobacteria have also been recovered from soil and appear to be a mixture of Gram-positive, Gram-negative and cell-wall-lacking species.[5][2] Ultramicrobacteria possess a relatively high surface-area-to-volume ratio due to their small size, which aids in growth under oligotrophic (i.e. nutrient-poor) conditions.[2] The relatively small size of ultramicrobacteria also enables parasitism of larger organisms;[2] some ultramicrobacteria have been observed to be obligate or facultative parasites of various eukaryotes and prokaryotes.[1][2] One factor allowing ultramicrobacteria to achieve their small size seems to be genome minimization[1][2] such as in the case of the ultramicrobacterium P. ubique whose small 1.3 Mb genome is seemingly devoid of extraneous genetic elements like nonworking genes, transposons, extrachromosomal elements etc.[2] However, genomic data from ultramicrobacteria is lacking[2] since the study of ultramicrobacteria, like many other prokaryotes, is hindered by difficulties in cultivating them.[3]

Ultramicrobacteria are commonly confused with ultramicrocells, the latter of which are the dormant, stress-resistant forms of larger cells that form under starvation conditions[1][2][6] (ie. these larger cells downregulate their metabolism, stop growing and stabilize their DNA to create ultramicrocells that remain viable for years[1][7]) whereas the small size of ultramicrobacteria is not a starvation response and is consistent even under nutrient-rich conditions.[3]

The term “nanobacteria” is sometimes used synonymously with ultramicrobacteria in the scientific literature,[2] but ultramicrobacteria are distinct from the purported nanobacteria or “calcifying nanoparticles”, which were proposed to be living organisms that were 0.1 μm in diameter.[8] These structures are now thought to be non-living,[9] and likely precipitated particles of inorganic material.[10][11]

See also
L-form bacteria
Mycoplasma – smallest known bacteria (300 nm)
Nanoarchaeum – smallest known archaeum (400 nm)
Nanobacteria – possible lifeforms smaller than bacteria (<200 nm)
Nanobe – possible smallest lifeforms (20 nm)
Pandoravirus – one of the largest known viruses (1000 nm)
Parvovirus – smallest known viruses (18–28 nm)
Pithovirus – largest known virus (1500 nm)
Prion – smallest known infectious agent (≈10 nm)
ND5 and MY14ᵀ – two aerobic, Gram-negative, rod-shaped bacteria[12]

 

Ultramikrobakterie – bakterie, które są znacznie mniejsze od typowych komórek bakteryjnych. Ich średnica waha się w granicach 0,2–0,3 μm. Termin ten został po raz pierwszy użyty w roku 1981 w odniesieniu do występujących w morskiej wodzie ziarenkowców, których średnica była mniejsza niż 0,3 μm[1]. Organizmy te zostały również odnalezione w glebie. Była to mieszanina gatunków zarówno Gram-dodatnich, jak i ujemnych[2]. Wiele, jeśli nie wszystkie, z tych bakterii to uśpione formy większych komórek. Pozwalają one przetrwać w niesprzyjających warunkach środowiska[3]. W tym stanie spoczynku komórki bakteryjne spowalniają swój metabolizm, wstrzymują wzrost i stabilizują DNA, tworząc uśpione, nierosnące komórki, które mogą pozostać żywe przez wiele lat[4]. Takie „formy głodowe” są prawdopodobnie najbardziej typowymi ultramikrobakteriami w wodzie morskiej[5].

Ultramikrobakteriami nie są „nanobakterie” („nanocząstki wapniejące”), struktury o średnicy 0,1 μm[6]. Chociaż ich zdolność do samoreplikacji oraz wywoływania chorób nie jest w pełni wyjaśniona, większość badań wyklucza ich przynależność do organizmów żywych[7]. Prawdopodobnie są to kompleksy mineralne powstające w wyniku wytrącania substancji nieorganicznych[8][9].

Zobacz też
przetrwalniki – formy spoczynkowe umożliwiające organizmom przetrwanie niekorzystnych dla nich warunków
nanoby – małe nitkowate struktury, które mogą być pozostałościami najmniejszych form życia

 

A nanobe is a tiny filamental structure first found in some rocks and sediments. Some scientists hypothesize that nanobes are the smallest form of life, 1/10 the size of the smallest known bacteria.[1]

No conclusive evidence exists that these structures are, or are not, living organisms, so their classification is controversial.

The 1996 discovery of nanobes was published in 1998[2] by Philippa Uwins et al.,[3] from the University of Queensland, Australia. They were found growing from rock samples (both full-diameter and sidewall cores) of Jurassic and Triassic sandstones, originally retrieved from an unspecified number of oil exploration wells off Australia's west coast. Depths of retrieval were between 3,400 metres (2.1 mi) and 5,100 metres (3.2 mi) below the sea bed. While Uwins et al. present assertions against it, they do not exclude the possibility that the nanobes are from a surface contaminant, not from the rock units cited.

The smallest are just 20 nanometers in diameter. Some researchers believe that these structures are crystal growths, but the staining of these structures with dyes that bind to DNA might indicate that they are living organisms.[4] They are similar to the structures found in ALH84001, a Mars meteorite found in the Antarctic. Nanobes are similar in size to nanobacteria, which are also structures that had been proposed to be extremely small living organisms. However, these two should not be confused. Nanobacteria were thought to be cellular organisms, while nanobes are hypothesized (by some) to be a previously unknown form of life or protocells.[citation needed]

Contents
1 Claims
2 Responses
3 See also
4 References
5 External links
Claims

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It is a living organism (contains DNA or some analogue, and reproduces).
Has a morphology similar to Actinomycetes and fungi.
Nanobes are about 20 nm in diameter, which may be too small to contain the basic elements for an organism to exist (DNA, ribosomes, etc.), suggesting that if they grow and reproduce they would need to do so in an unconventional way.
The Martian meteorite ALH84001, discovered in 1984 in the Antarctic, contained similar tubular structures which some astrobiologists suggested could be evidence of life at an earlier time on Mars.[5]
Responses
A review in Microbes and Environments[6] of the various ultra-small forms of proposed life states that the main criticism of nanobes is that they appear too small to contain the biochemical machinery needed to sustain life. The review also states that there is no evidence that nanobes are organisms in themselves and not fragments of larger organisms.

Tony Taylor was one of the authors of the original nanobe paper.[2] He argues that the conspicuous lack of phosphorus in the X-ray spectroscopy data and the failure to find DNA using various DNA amplification techniques demonstrates that nanobes do not have any DNA or RNA. He also argues that they may have a completely different mechanism for heredity, which would account for many of their unusual chemical and physical properties.

See also
Mycoplasma—smallest known bacteria (300 nm)
Nanoarchaeum—smallest known archaeum (400 nm)
Nanobacteria—possible lifeforms smaller than bacteria (<200 nm)
Pandoravirus—one of the largest known viruses (1000 nm)
Parvovirus—smallest known viruses (18–28 nm)
Pithovirus—largest known virus (1500 nm)
Prion—smallest known infectious agent (≈10 nm)
Protocell
Ultramicrobacteria—possible dormant forms of larger cells (200 nm)

 

Nanoby – małe, nitkowate struktury, odkryte po raz pierwszy w 1996 r. w skałach i osadach w Australii. Pewne hipotezy sugerują, że są to ślady najmniejszych form życia, dziesięć razy mniejszych niż najmniejsze znane dziś bakterie.

Odkrycie nanobów ogłosiła[1] Philipa Uwins[2] z Uniwersytetu Queensland w Australii.

Najmniejsze struktury mają 20 nanometrów średnicy. Niektórzy naukowcy uważają, że są to jedynie nieożywione formy krystaliczne, ale odnalezienie DNA w próbkach nanobów[3] może wskazywać na organizmy żywe. Ich morfologiczne struktury są zbliżone do struktur obserwowanych w marsjańskim meteorycie ALH 84001 znalezionym na Antarktydzie. Niektóre firmy biotechnologiczne zastanawiają się nad komercyjnym wykorzystaniem nanobów w utylizacji tworzyw sztucznych. Nanoby (podobnie jak nanobakterie) podejrzewane są o bycie patogenami, biorącymi udział w niektórych chorobach (np. w formowaniu się niektórych typów kamieni nerkowych). Próbuje się je także wiązać z mineralizacją zębów, co czyniłoby je ważnymi symbiontami[3].

Istnienie nanobów, podobnie jak nanobakterii, jest dość kontrowersyjne i wciąż brakuje na to przekonujących dowodów, jakkolwiek nie można mylić jednych z drugimi. W przeciwieństwie do nanobów, nanobakterie miałyby być otoczone ścianą – na wzór współcześnie znanych bakterii, podczas gdy nanoby miałyby stanowić całkowicie nową, wcześniej nieznaną grupę organizmów. Podobnie obie domniemane grupy są badane w różny sposób i odkryto je w innych okolicznościach.

Założenia
twory żywe, zawierające DNA lub jakieś jego analogi i reprodukujące się (niekoniecznie w sposób znany współczesnej biologii);
rosną swobodnie na podłożach nieorganicznych;
morfologicznie zbliżone do Actinomycetes i grzybów;
morfologicznie zbliżone do struktur obserwowanych w marsjańskim meteorycie ALH 84001, co mogłoby być dodatkowym dowodem na możliwość istnienia życia na Marsie;
brak dowodów i doniesień utożsamiających je z nanobakteriami, jakkolwiek wykazują z nimi pewne wspólne cechy.

 

In virology, defective interfering particles (DIPs), also known as defective interfering viruses, are spontaneously generated virus mutants in which a critical portion of the particle's genome has been lost due to defective replication or non-homologous recombination.[2][3] The mechanism of their formation is presumed to be as a result of template-switching during replication of the viral genome, although non-replicative mechanisms involving direct ligation of genomic RNA fragments have also been proposed.[4][5] DIPs are derived from and associated with their parent virus, and particles are classed as DIPs if they are rendered non-infectious due to at least one essential gene of the virus being lost or severely damaged as a result of the defection.[6] A DIP can usually still penetrate host cells, but requires another fully functional virus particle (the 'helper' virus) to co-infect a cell with it, in order to provide the lost factors.[7][8] DIPs were first observed as early as the 1950s by Von Magnus and Schlesinger, both working with influenza viruses.[9] However, the formalization of DIPs terminology was in 1970 by Huang and Baltimore when they noticed the presence of ‘stumpy’ particles of vesicular stomatitis virus in electron micrographs.[10] Defective Interfering Particles can occur within nearly every class of both DNA and RNA viruses both in clinical and laboratory settings including poliovirus, SARS coronavirus, measles, alphaviruses, respiratory syncytial virus and influenza virus.[11][12][13][14][15][16][17][18]

Contents
1 Defection
2 Interference
3 Pathogenesis
4 Types of defective RNA genomes
5 Recent published work
6 References
Defection
DIPs are a naturally occurring phenomenon that can be recreated under experimental conditions in the lab and can also be synthesized for experimental use. They are spontaneously produced by error-prone viral replication, something particularly prevalent in RNA viruses over DNA viruses due to the enzyme used (replicase, or RNA-dependent RNA polymerase.)[6][19] DI genomes typically retain the termini sequences needed for recognition by viral polymerases, and sequences for packaging of their genome into new particles, but little else.[20][21] The size of the genomic deletion event can vary greatly, with one such example in a DIP derived from rabies virus exhibiting a 6.1 kb deletion.[22] In another example, the size of several DI-DNA plant virus genomes varied from one tenth of the size of the original genome to one half.[23]

Interference
The particles are considered interfering when they affect the function of the parent virus through competitive inhibition[6] during coinfection. In other words, defective and non-defective viruses replicate simultaneously, but when defective particles increase, the amount of replicated non-defective virus is decreased. The extent of interference depends on the type and size of defection in the genome; large deletions of genomic data allow rapid replication of the defective genome.[20] During the coinfection of a host cell, a critical ratio will eventually be reached in which more viral factors are being used to produce the non-infectious DIPs than infectious particles.[20] Defective particles and defective genomes have also been demonstrated to stimulate the host innate immune responses and their presence during a viral infection correlates with the strength of the antiviral response.[11]

This interfering nature is becoming more and more important for future research on virus therapies.[24] It is thought that because of their specificity, DIPs will be targeted to sites of infection. In one example, scientists have used DIPs to create “protecting viruses”, which attenuated the pathogenicity of an influenza A infection in mice to a point that it was no longer lethal.[25]

Pathogenesis
DIPs have been shown to play a role in pathogenesis of certain viruses. One study demonstrates the relationship between a pathogen and its defective variant, showing how regulation of DI production allowed the virus to attenuate its own infectious replication, decreasing viral load and thus enhance its parasitic efficiency by preventing the host from dying too fast.[26] This also provides the virus with more time to spread and infect new hosts. DIP generation is regulated within viruses: the Coronavirus SL-III cis-acting replication element (shown in the image) is a higher-order genomic structure implicated in the mediation of DIP production in bovine coronavirus, with apparent homologs detected in other coronavirus groups.[1] A more in-depth introduction can be found in Alice Huang and David Baltimore's work from 1970.[27]

Types of defective RNA genomes
Deletions defections are when a fragment of the template is skipped. Examples of this type of defection can be found in tomato spotted wilt virus and Flock House virus.[28][29]
Snapbacks defections are when replicase transcribes part of one strand then uses this new strand as a template. The result of this can produce a hairpin. Snapback defections have been observed in vesicular stomatitis virus.[30]
Panhandle defections are when the polymerase carries a partially made strand and then switches back to transcribe the 5' end, forming the panhandle shape. Panhandle defections are found in influenza viruses.[31]
Compound defections are when both a deletion and snapback defection happens together.
Mosaic or complex DI genome, in which the various regions may come from the same helper virus genome but in the wrong order; from different helper genome segments, or could include segments of host RNA. Duplications may also occur.[3]
Recent published work
Recent work has been done by virologists to learn more about the interference in infection of host cells and how DI genomes could potentially work as antiviral agents.[3] The Dimmock & Easton, 2014 article explains that pre-clinical work is being done to test their effectiveness against influenza viruses.[32] DI-RNAs have also been found to aid in the infection of fungi via viruses of the family Partitiviridae for the first time, which makes room for more interdisciplinary work.[19]

Several tools as ViReMa[33] and DI-tector [34] have been developed to help to detect defective viral genomes into next-generation sequencing data.

 

Virus-like particles (VLPs) are molecules that closely resemble viruses, but are non-infectious because they contain no viral genetic material. They can be naturally occurring or synthesized through the individual expression of viral structural proteins, which can then self assemble into the virus-like structure.[1][2][3][4] Combinations of structural capsid proteins from different viruses can be used to create recombinant VLPs.VLPs derived from the Hepatitis B virus and composed of the small HBV derived surface antigen (HBsAg) were described in 1968 from patient sera.[5] VLPs have been produced from components of a wide variety of virus families including Parvoviridae (e.g. adeno-associated virus), Retroviridae (e.g. HIV), Flaviviridae (e.g. Hepatitis C virus) , Paramyxoviridae (e.g. Nipah) and bacteriophages (e.g. Qβ, AP205).[1] VLPs can be produced in multiple cell culture systems including bacteria, mammalian cell lines, insect cell lines, yeast and plant cells.[6][7]

Contents
1 Applications
1.1 Virus research
1.2 Therapeutic and Imaging Agents
1.3 Vaccines
1.4 Mycoviruses
1.5 Lipoparticle technology
2 Expression Host Systems
3 Assembly
4 Linking targeting groups to VLP surfaces
5 Purification of non-enveloped VLPs
6 References
7 External links
Applications
Virus research
VLPs are used in studies to identify viral protein components.

Therapeutic and Imaging Agents
VLPs are a candidate delivery system for genes or other therapeutics.[8] These drug delivery agents have been shown to effectively target cancer cells in vitro.[9] It is hypothesized that VLPs may accumulate in tumor sites due to the enhanced permeability and retention effect, which could be useful for drug delivery or tumor imaging [10]

Vaccines
VLPs are useful as vaccines. VLPs contain repetitive, high density displays of viral surface proteins that present conformational viral epitopes that can elicit strong T cell and B cell immune responses.[11] Since VLPs cannot replicate, they provide a safer alternative to attenuated viruses. VLPs were used to develop FDA-approved vaccines for Hepatitis B and human papillomavirus.[12] More recently, VLPs were used to develop a pre-clinical vaccine against chikungunya virus.[11]

Research suggests that VLP vaccines against influenza virus could provide stronger and longer-lasting protection against flu viruses than conventional vaccines.[13] Production can begin as soon as the virus strain is sequenced and can take as little as 12 weeks, compared to 9 months for traditional vaccines. In early clinical trials, VLP vaccines for influenza appeared to provide complete protection against both the Influenza A virus subtype H5N1 and the 1918 flu pandemic.[14] Novavax and Medicago Inc. have run clinical trials of their VLP flu vaccines.[15][16]

Mycoviruses
Some fungi contain mycoviruses that lack the ability to be transmitted in cell free preparations and may be classified as VLPs. These are important in phytopathology, as they can cause hypovirulence in some species of phytopathogenic fungi.[citation needed]

Lipoparticle technology
The VLP Lipoparticle was developed to aid the study of integral membrane proteins.[17] Lipoparticles are stable, highly purified, homogeneous VLPs that are engineered to contain high concentrations of a conformationally intact membrane protein of interest. Integral Membrane proteins are involved in diverse biological functions and are targeted by nearly 50% of existing therapeutic drugs. However, because of their hydrophobic domains, membrane proteins are difficult to manipulate outside of living cells. Lipoparticles can incorporate a wide variety of structurally intact membrane proteins, including G protein-coupled receptors (GPCR)s, ion channels and viral Envelopes. Lipoparticles provide a platform for numerous applications including antibody screening, production of immunogens and ligand binding assays.[18] [19]

Expression Host Systems
The first step to creating a VLP is cloning and expressing the structural genes of interest.[1] There are many systems to choose for expression. The chosen expression system can determine the limitations and effectiveness of the resulting VLP. The most well established expression systems being used today are as follows:

Bacterial systems are one of the most widely used, and are often based on the very well studied bacteria, Escherichia coli.[1] This is a preferred method for production of recombinant proteins on a global scale due to the low cost and rapid nature of production, ease of scaling up, and high levels of expression.[7] It is also possible to construct a VLP with multiple types of structural proteins. However, there are several disadvantages that come with use of this system:

Inability to produce post-translational modifications[1]
Inability to generate proper disulfide bonds within proteins[1]
Other recombinant proteins of interest, particularly from eukaryotic cells, may be insoluble in an E. colisystem[1]
Presence of endotoxins in generated proteins[1][20]
Research has suggested that culturing the cells at a low temperature or use of a fusion protein system can increase solubility for other proteins.[1]

Yeast systems have been used to express structural genes of bacterial, yeast, plant and mammalian origin.[1] Unlike bacterial systems, it is possible to introduce post-translational modifications and there is no endotoxin presence. Another disadvantage is that this system only allows for the creation of non-enveloped viruses.[1] Yeast expression is unique in two ways: 1) to successfully produce a VLP using a yeast expression system, the bacteria must be propagated in bacteria before being introduced to the cell to create a stable transgene product[1] and 2) Research has suggested that VLP assembly may occur more efficiently during the purification stage, instead of the cultivation stage.[1] Pichia and Hansenulaare the most commonly used yeast strains.

Insect cell systems have fast growth rates in media without animal products, capacity for large scale cultivation, and the possibility of introducing post translational modifications. A baculovirus vectors always needs to succesfuly create the VLP[1][20]. If more than one protein is required, the cell can be coinfected with a polycistronic vector, or infected with multiple monocistronic vectors. The latter method is preferred, because it allows for manipulation of individual protein levels, and identification of which ones are necessary.[1] Although glycosylationis present, the patterns differ from that of mammalian cells, leading to a slightly different product.[21]

Plant systems are less popular, but are good for the creation of VLPs with specific characteristics.[1] Initially, plant-based expression systems gained popularity because they were attached to the idea of edible vaccines. It was thought that if an antigen was recombinantly expressed in a plant, ingestion of it would cause an immune response and effectively vaccinate the patient.[22] Research has since moved away from edible vaccines for several reasons: administration of the vaccine by a medical professional is more likely to yield reproducible results,[1] oral delivery was found to provide some protection against enteric pathogens, but not with any other body system[22], lack of antigen accumulation in the plant[22], and the avoidance of digestive acid and degrading enzymes[22].

The gene(s) for the protein(s) of interest are most commonly introduced using Agrobacterium[1][22].Once introduced, the gene can incorporate in either the nuclear or chloroplast genome.[6] Although chloroplast transformation leads to very high copy numbers, it is a prokaryotic genome, so no glycosylation is observed[22]. Genetic material can be introduced into the capsid during or after its assembly.[23]

Mammalian systems are one of the most popular choices for researchers, making more than half of the recombinant proteins used in the pharmaceutical industry.[1] While the complexity of construction and applications can often be a problem, it also leads to expression of highly efficient, high quality, complex VLPs that also have the correct glycosylation pattern.[24][20][25]This system is useful for using a single polycistronic vector, as described above for the insect expression system. The recombinant VLPs are usually achieved using one of two methods:[25]

Adhesion Culture – cells are seeded onto a surface and given proper nutrients
Suspension Culture – cells are grown suspended in some type of culture media
The latter method is more widely used when using mammalian cells to create VLPs.[25]

Cell-Free Protein Systems (CFPS) are sometimes used to create VLPs. The following CFPS are commercially available: E. coli, wheat germs, insect cells, and rabbit reticulocytes.[25]

Assembly
The understanding of self-assembly of VLPs was once based on viral assembly. This is rational as long as the VLP assembly takes place inside the host cell (in vivo), though the self-assembly event was found in vitro from the very beginning of the study about viral assembly.[26] Study also reveals that in vitro assembly of VLPs competes with aggregation[27] and certain mechanisms exist inside the cell to prevent the formation of aggregates while assembly is ongoing.[28]

Linking targeting groups to VLP surfaces
Attaching proteins, nucleic acids, or small molecules to the VLP surface, such as for targeting a specific cell type or for raising an immune response is useful. In some cases a protein of interest can be genetically fused to the viral coat protein.[29] However, this approach sometimes leads to impaired VLP assembly and has limited utility if the targeting agent is not protein-based. An alternative is to assemble the VLP and then use chemical crosslinkers,[30] reactive unnatural amino acids[31] or SpyTag/SpyCatcher reaction[32][33] in order to covalently attach the molecule of interest. This method has shown to be very effective at directing the immune response against the attached molecule, thereby inducing high levels of neutralizing antibody titres and breaking immune self-tolerance.[33]

Purification of non-enveloped VLPs
After the proteins of interest have been cloned and expressed in one of the above mentioned systems, they must be purified to get the final VLP product. Purification of non-enveloped VLPs generally involves four basic steps:

Cell Lysis – cells are broken to release VLPs into solution[1]
Cell Clarification – cellular debris is removed, leaving behind VLPs
Cell Concentration – The cell lysate (in this case, VLPs) are brought up to higher concentration in solution[34]
Cell Polishing – removal of residual impurities[34]
These steps can be repeated multiple times in cycles depending on which protocol is used.

 

 

 

Subcellular Life Forms
John Baez
August 12, 2017
Also available in PDF, Postscript and LaTeX, thanks to Stephen Mulraney. Alas, I have drastically updated the 1998 version of this webpage, but these revisions are not yet included in the PDF, Postscript and LaTeX files.
I like biology, but as a mathematician I am drawn to the elegance of the very simplest forms of life: the subcellular life forms. They are so simple, in fact, that even calling them “alive” can be controversial. They lack many of the usual features of life. They don’t have cell walls, most of them don’t metabolize, and they are all parasitic, depending on other organisms for their ability to reproduce! Some of them even have no genetic code! Many of them cause diseases, but others are crucial to the well-being of their host, and many are so well integrated with their host that it becomes difficult to decide whether they are part of the host or a separate entity.

Indeed, besides my love of elegance and my morbid fascination with parasites, the main reason subcellular life forms appeal to me is that they challenge our naive notion of organisms as entities with clear, well-defined boundaries. It’s clear by now that life doesn't respect this simple picture. Whenever a pattern of any sort, however abstract, is able to replicate itself, it does! Typically these patterns overlap and interact in subtle ways, so one can't easily say where one ends and the other begins.

These are the main kinds of subcellular life forms that I know about so far:

Viruses
Viroids
Satellites
Plasmids
Transposons
Prions
I'll say a little about each kind.
I am just beginning to learn about

Mycoplasmas
and
Nanobacteria
which are not exactly “subcellular”, but still interesting – and controversial!
it’s hard to classify these life forms, since they don’t all have “species” in the usual sense, and they don’t fit into the standard “kingdoms” of cellular life – a classification scheme which is itself somewhat outdated. In my first attempts to understand the taxonomy of subcellular life, I was greatly aided by Diener and Prusiner's 1987 article The recognition of subviral pathogens [MM]. But in subsequent decades knowledge of these creatures has grown vastly, thanks to work on biotechnology. Now there's even a special committee devoted to their classification, called the International Committee on Taxonomy of Viruses (though they also tackle some other subcellular life forms). They even have a nice online database explaining their classification scheme.

But beware! People still argue about the correct classification of subcellular life forms. That's part of what's interesting about them: they really stretch our ideas in biology to the breaking point.

One thing to keep in mind: these life forms are small. Remember that DNA is a double helix containing information in the form of AT and CG “base pairs” – that is, paired molecules of adenine and thymine, or cytosine and guanine. Single-stranded RNA is a single helix containing information in the form of A, U, C, and G “bases” – molecules of adenine, uracil, cytosine and guanine. The human genome is made of DNA and contains about 5 billion base pairs. The genome of a bacterium is also made of DNA but has less than 10 million bases. The potato spindle tuber viroid, on the other hand, is nothing but a circular loop of RNA consisting of 359 bases! Small, simple – but effective!

The potato spindle tuber viroid is the smallest naturally self-replicating bit of RNA. “Spiegelman’s Monster” is even smaller – it consists of just 220 bases! But this entity survives only under artificial conditions. The story of this monster is fascinating. Here is Paul Davies' [Da] account of it:

The Qb virus doesn't need anything as complicated as a cell in order to replicate: a test tube full of suitable chemicals is enough. The experiment, conducted by Sol Spiegelman of the University of Illinois, consisted of introducing the viral RNA into a medium containing the RNA's own replication enzyme, plus a supply of raw materials and some salts, and incubating the mixture. When Spiegelman did this, the system obligingly replicated the strands of naked RNA. Spiegelman then extracted some of the freshly synthesized RNA, put it in a separate nutrient solution, and let it multiply. He then decanted some of that RNA into yet another solution, and so on, in a series of steps.
The effect of allowing unrestricted replication was that the RNA that multiplied fastest won out, and got passed on to the “next generation” in the series. The decanting operation therefore replaced, in a highly accelerated way, the basic competition process of Darwinian evolution, acting directly on the RNA. In this respect it resembled an RNA world.

Spiegelman’s results were spectacular. As anticipated, copying errors occurred during replication. Relieved of the responsibility of working for a living and the need to manufacture protein coats, the spoon-fed RNA strands began to slim down, shedding parts of the genome that were no longer required and merely proved to be an encumbrance. The RNA molecules that could replicate the fastest simply out-multiplied the competition. After seventy-four generations, what started out as an RNA strand with 4,500 nucleotide bases ended up as a dwarf genome with only 220 bases. This raw replicator with no frills attached could replicate very fast. It was dubbed Spiegelman’s monster.

Incredible though Spiegelman’s results were, an even bigger surprise lay in store. In 1974, Manfred Eigen and his colleagues also experimented with a chemical broth containing Qb replication enzyme and salts, and an energized form of the four bases that make up the building blocks of RNA. They tried varying the quantity of viral RNA initially added to the mixture. As the amount of input RNA was progressively reduced, the experimenters found that, with little competition, it enjoyed untrammeled exponential growth. Even a single RNA molecule added to the broth was enough to trigger a population explosion. But then something truly amazing was discovered. Replicating strands of RNA were still produced even when not a single molecule of viral RNA was added! To return to my architectural analogy, it was rather like throwing a pile of bricks into a giant mixer and producing, if not a house, then at least a garage. At first Eigen found the results hard to believe, and checked to see whether accidental contamination had occurred. Soon the experimenters convinced themselves that they were witnessing for the first time the spontaneous synthesis of RNA strands form their basic building blocks. Analysis revealed that under some experimental conditions the created RNA resembled Spiegelman’s monster.

In 1997, further experiments by Eigen and Oehlenschlager [EO] showed that Spiegelman’s monster eventually evolves (under the same unnatural conditions) to two kinds of RNA, one consisting of 54 bases and one consisting of only 48!

One thing this shows is that viruses will always evolve towards becoming smaller if it helps them reproduce faster. Experiments by Turner [T] have shown that viruses will gladly “cheat” and drop some of their genes if there are enough other viruses of the same sort around doing the work these genes allow. This leads to some interesting problems in game theory, related to the so-called Prisoner's Dilemma. This tendency of viruses to shrink to the bare minimum may explain how satellites came into existence.

By the way: please email me if you find mistakes in this webpage, or if you know any more fascinating facts about subcellular life forms – especially if you know kinds that aren't on this list! It will take me a long time to reply, but I eventually will. I would like to thank Daniele Focosi for doing this, and urge everyone to look at his webpage on the physiology of subcellular life forms. I also thank Axel Boldt.

Viruses
Diener and Prusiner define a virus to be a “small infectious pathogen composed of one or more nucleic acid molecules usually surrounded by a protein coat.” They typically reproduce by latching onto the wall of a cell and inserting their genetic material – i.e., the nucleic acids – into the cell. This genetic material then uses the cell's machinery to make more copies of the virus. Typically, these copies overrun the cell until it bursts. However, the actual life cycle of a virus is often more complicated than this thumbnail sketch! Viruses use a large number of sneaky tricks to overcome the defense mechanisms of the cell.

Apart from their intrinsic interest, viruses are important because they cause many diseases among humans, such as:

the common cold
influenza (the flu)
measles
rubella
mumps
warts
chickenpox
smallpox
acquired immunodeficiency syndrome (AIDS)
herpes
hepatitis
rabies
poliomyelitis (polio)
encephalomyelitis
encephalitis
yellow fever
dengue fever
West Nile fever
as well as diseases of domesticated animals and plants. For a detailed tour, try The Big Picture Book of Viruses, available online. For even more information, try the chapter on virology prepared by Margaret and Richard Hunt as part of a wonderful online textbook called Microbiology and Immunology.

There is by now a standard taxonomy of viruses [F], [CT] [Ma2], [Re]. Here, however, I will content myself with a rough classification of viruses into following 3 sorts:

DNA viruses
RNA viruses
and

Reverse transcribing viruses
DNA viruses
The genome of a DNA virus is a single molecule of DNA, either linear or circular. Outside the host cell, this DNA is usually surrounded by a protein coat. There are 5 known families of DNA viruses affecting humans. The size and structure of the DNA viruses varies widely, from small ones with only 5,000 base pairs to the large brick-shaped or ovoid pox viruses, which have a lipid coating and whose DNA has between 120,000 and 360,000 base pairs.

One can broadly classify the DNA viruses into two kinds:

double-stranded DNA viruses
single-stranded DNA viruses
If you click on the options above you'll see that most known DNA viruses are double-stranded, including all the DNA viruses that affect humans.

RNA viruses
The genome of an RNA virus is usually a single molecule of RNA, either linear or circular, but some contain up to a dozen molecules of RNA. Outside the host cell, this RNA is protected by a protein coat. Most viruses are RNA viruses. There are 13 known families of RNA viruses affecting humans. RNA viruses range widely in morphology and size, with their genome containing anywhere from 1,700 to 60,000 nucleotides.

The smallest RNA virus, the hepatitis delta agent (HDV), is quite different from all the rest. With only about 1,700 nucleotides, its genome is much smaller than that of any other virus. Like a virusoid, it’s a circular loop of RNA that can only reproduce in cells infected by a helper virus, the hepatitis B virus. But unlike a virusoid, it codes for its own protein coat. Its genome is also much bigger than those of virusoids, which have only about 350 nucleotides. In these ways it’s more like a viroid. However, viroids only infect plants!

One can broadly classify RNA viruses into:

double-stranded RNA viruses
positive-sense RNA viruses
negative-sense RNA viruses
A “positive-sense” RNA virus consists of single-stranded RNA that functions directly as messenger RNA in the host cell, so that ribosomes in the host cell synthesize various proteins needed by the virus when encountering this RNA. A “negative-sense” RNA virus consists of single-stranded RNA that does not function as messenger RNA, since it contains the complementary base pairs. Negative-sense RNA viruses carry enzymes with them into the host cell to synthesize messenger RNA from the RNA in the virus. “Double-stranded” RNA viruses have both positive-sense and negative-sense strands. For some reason these are more likely to consist of several separate pieces of RNA. If you click on the options listed above, you'll see examples of these different kinds of RNA viruses.

Reverse transcribing viruses
Reverse transcribing viruses behave quite differently from the other viruses described above. There are two main kinds of reverse transcribing viruses:

RNA reverse transcribing viruses (retroviruses)
DNA reverse transcribing viruses
If you click on these options you'll see examples of both kinds.
RNA reverse transcribing viruses are usually called “retroviruses”. They have a single-stranded RNA genome. They infect animals, and when they get inside the cell's nucleus, they copy themselves into the DNA of the host cell using reverse transcriptase. In the process they often cause tumors, presumably by damaging the host's DNA.

Retroviruses are important in genetic engineering because they raised for the first time the possibility that RNA could be transcribed into DNA, rather than the reverse. In fact, some of them are currently being deliberately used by scientists to add new genes to mammalian cells.

Retroviruses are also important because AIDS is caused by a retrovirus: the human immunodeficiency virus (HIV). This is part of why AIDS is so difficult to treat. Most usual ways of killing viruses have no effect on retroviruses when they are latent in the DNA of the host cell.

From an evolutionary viewpoint, retroviruses are fascinating because they blur the very distinction between host and parasite. Their genome often contains genetic information derived from the host DNA. And once they are integrated into the DNA of the host cell, they may take a long time to reemerge. In fact, so-called “endogenous retroviruses” can be passed down from generation to generation, indistinguishable from any other cellular gene, and evolving along with their hosts, perhaps even from species to species! It has been estimated that up to 1% of the human genome consists of endogenous retroviruses! Furthemore, not every endogenous retrovirus causes a noticeable disease. Some may even help their hosts [LA], [V].

It gets even spookier when we notice that once an endogenous retrovirus lost the genes that code for its protein coat, it would become indistinguishable from an LTR retrotransposon – one of the many kinds of “junk DNA” cluttering up our chromosomes. Just how much of us is made of retroviruses? it’s hard to be sure.

So much for retroviruses… what about DNA reverse transcribing viruses? These have a DNA genome, and instead of reverse transcriptase copying the RNA of the free-floating virus to the DNA of the host, they work the other way around. When they've infected the host cell, there is a lot of RNA floating around; they use reverse transcriptase to package themselves as DNA when they leave the cell!

There aren't many DNA reverse transcribing viruses. Most of them are relatives of the hepatitis B virus (HBV). This virus attacks liver cells, and can cause tumors. Unlike a typical DNA virus, the hepatitis B virus consists of both single-stranded and double-stranded DNA. it’s also smaller than any DNA virus: its nucleotide consists of only about 2,400 base pairs.

I wonder why the viruses affecting the liver are so strange and diverse. The hepatitis B virus is quite unusual, and I've already mentioned its even more bizarre symbiote (or parasite): the hepatitis delta agent (HDV), which is the smallest RNA virus, and different from all the rest. There are also four other forms of hepatitis: positive-sense RNA viruses called HAV, HCV, HEV, and HGV. None of these are in the same family! Apparently all they have in common is that they attack the liver.

Viroids
A viroid is defined to be a “small infectious pathogen composed entirely of a low molecular weight RNA molecule”. Thus, unlike a virus, a viroid has no protein coat. It is nothing but a single-stranded circular loop of RNA! Most viroids consist of about 250 to 375 nucleotides, much smaller than a typical virus. Also, viroids don’t function as messenger RNAs, so they don’t make the cell synthesize enzymes: they rely completely on pre-existing enzymes in the host for their reproduction.

Most known viroids cause diseases in plants. The first viroid was discovered in 1971, by Diener. it’s called the potato spindle tuber virus (PSTV), since it causes a disease that makes potatos abnormally long and sometimes cracked. At the time, Diener's isolation of the viroid causing this disease met with some skepticism, since it was so much smaller than any known virus. By 1991, however, at least 15 plant diseases had been traced to viroids. There are also 2 viroids known, the hop latent viroid (HLV) and a viroid living in grapevines, that cause no known symptoms! This raises the fascinating possibility that there could be more such viroids lurking around.

The complete molecular structure of many viroids has been worked out, which has allowed a classification of viroids on the basis of their RNA sequences. Roughly speaking, there are a large family of viroids that share many features with PSTV, together with one viroid that seems very different: the avocado sunblotch viroid (ASBV). McInnes and Simons have proposed a further classification of the PSTV-type viroids into three kinds [Ma1].

It is clear from these RNA sequences that viroids are not “degenerate viruses”, as had once been thought. They are quite different from any known viruses. One interesting theory is that they arose from RNA that escaped from cell nuclei.

it’s also interesting that all viroid diseases have been detected in the 20th century, some quite recently – in contrast to diseases caused by viruses. Also, many viroid diseases have been spreading after their discovery, often due to human activity. A fascinating example is the coconut cadang-cadang viroid (CCCV), a disease of coconuts which has been spreading throughout the Phillipines. On the island of Luzon, a puzzling feature of this disease was that it only affected crops owned by speakers of Bicalano, while adjacent crops owned by speakers of Tagalog went unharmed! Eventually people realized that the viroids were spread by workers cutting the palms. Tagalog owners prefer to hire Tagalog workers, while Bicalanos hire Bicalanos, some of whom came from an area where the disease was prevalent. (See the article by Maramarosch entitled The cadang-cadang viroid disease of palms [Di].)

Because of this sort of epidemiology, Diener has suggested that viroids may be latent to their native host plants (like HLV), becoming pathogenic only when transferred to other species thanks to agriculture. Indeed, the viroid causing tomato “planta macho” disease in Mexico, TPMV, has also been found in wild plants there. Also, an avocado plant will sometimes seem to “recover” from ASBV by sending up a new shoot. This new shoot is still infected with the viroid, but it shows no symptoms other than reduced fruit yield. Descendants of such a “recovered” tree are also infected with the viroid, and also symptomless, except for reduced fruit yield. Thus the avocado appears able to “come to terms” with the viroid in some way. Personally, I'd like to raise this possibility: that some viroids actually play a beneficial role in their native host plants! This may seem surprising, but when we compare the behavior of plasmids, it may seem less so.

Satellites
A satellite is a “sub-viral agent composed of nucleic acid molecules that depends for its reproduction on co-infection of a host cell with a helper virus”. In other words, just as a planet can have a moon orbiting it, a virus can have a satellite orbiting it!

There are various kinds of satellites:

Satellite viruses
Satellite nucleic acids
Satellite DNAs
Double-stranded satellite RNAs
Single-stranded satellite RNAs
A “satellite virus” is a satellite whose genome codes for the protein coat in which it is encapsidated. All known satellite viruses have a genome made of single-stranded RNA. There are only five known kinds. A good example is the tobacco mosaic satellite virus, which goes along with the well-known tobacco mosaic virus (TMV).

A “satellite nucleic acid” is a satellite whose genome does not code for a protein coat; instead, it hides in the protein coat of its virus helper! A satellite nucleic acid can consist of either DNA or RNA. All known satellite DNAs are single-stranded, but satellite RNAs can be single- or double-stranded.

Single-stranded satellite RNAs are fascinating because they include the very smallest forms of life known – the virusoids! These are circular loops of single-stranded RNA containing about 350 nucleotides. They can only reproduce in cells that have been infected by their helper virus, because they use some of the RNA of the helper virus to reproduce. The helper virus is typically an RNA virus which causes a disease of plants and consists of about 4500 nucleotides.

One might be tempted to say that a virusoid is a parasite of its helper virus. But it’s not always so simple. Sometimes the helper virus is unable to reproduce unless the virusoid is present! Then we have symbiosis rather than parasitism.

The first virusoids were discovered in the early 1980s in Australia, associated with viruses causing diseases such as velvet tobacco mottle (VTMoV), solanum nodiflorum mottle (SNMV), lucerne transient streak (LTSV), and subterranean clover mottle (SCMoV).

An interesting theory about the origin of virusoids is that in plants infected with both viruses and viroids, the viroids got encapsidated in the viruses and later lost their ability to reproduce independently.

An easy way to learn more about viroids and satellites is to read the online course notes by the plant pathologist Zhongguo Xiong. In fact, if you like subcellular life forms, his whole course on plant virology is worth reading!

Plasmids
A plasmid is a “small autonomously replicating circular molecule of DNA that is devoid of protein and not essential for the survival of its host”. Plasmids range in size greatly, from about 4350 to 240,000 base pairs. Most known plasmids infect bacteria, but some infect plant and animal cells. They often copy themselves into the DNA of the host cell, and many carry genetic traits from one cell to another. Most plasmids keep a limit on the number of copies of themselves they keep in each host – the so-called “copy number”, which ranges from 1 to about 40. Many plasmids are “conjugative”. This means they can transfer copies of themselves from one host to another by forcing the host to undergo “conjugation” – a form of sex in which genetic material is exchanged between bacteria.
People tend not to speak of plasmids as “life forms” quite as often as they do with viruses. In part this may be because plasmids are sometimes beneficial to their host cells, rather than pathogenic.

However, is difficult for me to resist the impression that plasmids are just as “alive” as viruses. Indeed, some viruses become plasmids when parts of them are missing! For example, the “lambda bacteriophage” is a virus that infects the intestinal bacterium E. coli, but “lambda dv particles”, which arise from the lambda phage simply by deleting some DNA, are plasmids. The lambda phage multiplies inside its host and then kills it by “lysis”, which destroys the cell membrane and releases lots of copies. The lambda dv particles, on the other hand, stays in the cell in a fairly stable number of copies and does not kill its host. The difference is that while the lambda dv particles contain genes for replication, they lack genes for lysis and the protein coat.

If we think of plasmids as life forms, we must admit that they are very successful. Many plasmids spread so thoroughly in cultures of bacteria that less than one cell in 100,000 lacks a copy! Some kinds of plasmids contain genes that help make sure copies are efficiently passed on to both daughter cells when the host cell divides. F plasmids have a particularly clever mechanism – they temporarily inhibit cell division when they have not yet replicated inside the host!

Plasmids are diverse and very interesting. Some important kinds are:

R Plasmids
F Plasmids
Colicin Plasmids
Virulence Plasmids
Metabolic Plasmids
Tumor-Causing Plasmids
and

Cryptic Plasmids
While they don’t quite fit under this heading, I can't resist also mentioning
Cosmids
and

Phasmids
These are man-made entities based on plasmids, used in biotechnology. Are they alive? You judge.

Some good books on plasmids include Plasmids by Paul Broda [B], Bacterial Plasmids by Kimber Hardy [H], and Plasmids of Eukaryotes: Fundamentals and Applications by K. Esser et al [E].

R Plasmids
R plasmids were first discovered in Japan in 1957. In Japan, dysentery was treated with sulphonamide until about 1950. Then, more and more strains of the bacteria causing dysentery became resistant to this antibiotic, rapidly rendering it ineffective. Doctors then began using tetracycline, streptomycin and chloramphenicol. By 1957, 2% of the bacteria causing dysentery were resistant to one or more of these drugs, and by 1960, 13% were resistant. It turned out that R plasmids were the culprit!

R plasmids contain genes that give their bacterial hosts resistance to antibiotics as well as to poisonous metal ions such as arsenic, silver, copper, mercury, lead, zinc and so on. Because many R plasmids are conjugative, this resistance can spread from one bacterium to another. Because they can live in more than one species of bacteria, R plasmids can also spread resistance between bacteria of different species!

Spread of resistance to antibiotics is now a major problem in medicine. Drugs which were used for many years to control bacterial diseases are now becoming helpless against new resistant strains. The problem has been made worse by the tendency for doctors and veterinarians to use antibiotics when they aren't strictly necessary, for example as part of livestock food. As a result an environment is created where bacteria with resistance have a great competitive advantage, so they spread rapidly.

It has also recently been found that weeds growing near crops that were genetically engineered to resist herbicides can acquire this trait. I'm not sure, but I suspect that this happens via plasmids as well.

R plasmids make it clear that the idea of evolution as a battle between species with separately evolving genomes is a great oversimplification. Instead, genetic communication and cooperation between different species can be very important.

F Plasmids
F plasmids live in the bacterium E. coli and were discovered in the 1920s. An F plasmid contains genes that make the cell membrane of its host form long tubes. These tubes, called “sex pili”, attach themselves to other E. coli and puncture their cell membranes. The F plasmid then duplicates and a copy passes from the original host to the new host. A clever system has evolved to ensure that the sex pili of a given bacterium never attach to itself.

F plasmids give their hosts no known traits besides these sex pili. The evolutionary origins of sex are much debated these days; we see here the fascinating possibility that sex can originate as a kind of disease whose sole function is to spread a parasite!

Colicin Plasmids
Colicin plasmids contain genes that give their host bacterium a certain small probability of bursting open and releasing chemicals called “colicins”. These chemicals kill other bacteria by rendering their cell membranes permeable to important ions. There are many strains of colicin plasmid. Each one confers immunity only to the particular sort of colicin it produces. Different strains of colicin plasmid are “incompatible”, meaning that a given strain bacterium cannot stably contain both.

In short, different strains of colicin plasmid compete with each other using the resources of their hosts. A colicin plasmid will confer an advantage to its host bacteria if the other strains of bacteria nearby do not have a colicin plasmid. However, when there are many different strains of colicin plasmid present, all strains of host bacteria suffer. Thus there is a certain similarity between colicin plasmids and “protection rackets” run by Mafia-like gangs.

Colicin plasmids are not the only sort of plasmids that exhibit incompatibility. Similar plasmids tend to be incompatible with each other, while drastically different plasmids are usually compatible. One theory is that incompatible plasmids use the same mechanisms to maintain their copy number. In a cell containing two incompatible sorts of plasmid, their reproduction is blocked until the total number of copies of the two together drops to the copy number of each one. This is an unstable situation, especially for plasmids with a low copy number, so eventually descendants of the host cell contain only one or the other plasmid.

Virulence Plasmids
Virulence plasmids contain genes that make their bacterial hosts more virulent to their hosts. A familiar example involves the bacterium E. coli, which inhabits the human large intestine. Certain strains of E. coli contain plasmids whose genes make the E. coli synthesize toxins that cause diarrhea. These “enterotoxigenic strains” of E. coli are probably an important cause of diarrhea among travellers. More seriously, in developing countries, diarrhea is one of the principal causes of death among those under five.

“Vibrio cholerae”, the cause of cholera, is a bacterium whose genes code for a diarrhea-causing toxin. The DNA of these genes is closely related to the DNA of certain virulence plasmids infecting E. coli – so closely that there is almost certainly a common ancestor. For example, Vibrio cholerae could have evolved from an earlier bacterium by permanently integrating the DNA from a virulence plasmid into its genome.

Strains of bacteria and viruses often become less virulent as they coevolve with their hosts. Thus one may wonder what evolutionary advantage a virulence plasmid could confer to the bacteria containing it. In the case of bacteria causing diarrhea, there is an obvious possibility: diarrhea can serve as a mechanism for spreading the bacteria – and their plasmids – that cause it!

Metabolic Plasmids
Metabolic plasmids contain genes that let their bacterial hosts metabolize or degrade otherwise indigestible or toxic chemicals. For example, the bacterium Pseudomonas putida is able to grow on a wide range of organic compounds that are toxic to most bacteria, including toluene, octane, camphor, napthalene and nicotinic acid! It does this with the help of genes contained by metabolic plasmids called TOL, OCT, CAM, NAH and NIC plasmids.

it’s worth noting that some of these chemicals are secreted by plants as part of a defense against bacteria. Thus we probably have a kind of natural chemical arms race going on here. Other metabolic plasmids allow bacteria to degrade herbicides like 2,4-D, as well as certain detergents! People are investigating the use of such plasmids to help biodegrade pollution.

Tumor-Causing Plasmids
“Crown gall” is a cancer of plants caused by a bacterium known as Agrobacterium tumefaciens. But actually, the disease is caused by a plasmid having this bacterium as its host! When the plasmid passes from the bacterium to the cells of infected fruit trees, some of the genes contained in the plasmid cause tumors. Do these tumors help spread the bacteria to other trees?

Cryptic Plasmids
Cryptic plasmids are plasmids that have no known effect on their hosts. How much of this is our ignorance, and to what extent is being truly “cryptic” a successful strategy?

Cosmids
Cosmids are man-made circular loops of DNA containing plasmid DNA together with an arbitrary sequence of up to 45,000 base pairs of DNA. They are constructed by recombinant DNA techniques and then packaged in lambda phage protein coats. They are used to transfer genes to bacteria.

The lambda phage is a virus that specializes in invading bacteria such as E. coli. In nature, its protein coat latches onto the bacterial cell membrane and injects the phage DNA into the bacterium. Biotechnologists have taken advantage of this by using the lambda phage protein coat to inject a cosmid into the bacterium! Once inside, the cosmid replicates like a plasmid and, like a plasmid, integrates its DNA into the genome of the bacterium.

Phasmids
Phasmids are man-made linear DNA molecules whose ends are sequences taken from the lambda phage, while the middle is a sequence taken from a plasmid, together with a sequence of whatever DNA one wants. Like cosmids, they are constructed by recombinant DNA techniques and packaged in lambda phage protein coats, and used to transfer genes to bacteria. However, both the lambda phage and plasmid replication functions are intact. In particular, they contain the lambda phage genes for “lysis”, the process whereby a virus dissolves the cell membrane of its host. Depending on the conditions, the phasmid can act either like a phage or a plasmid – hence its name.

Transposons
Transposons, or “transposable elements”, are sequences of DNA that move within their host's genome from one position to another. They were first discovered in the 1940s by Barbara McClintock, who later won the Nobel prize for this work. They exist in all known organisms, often in large quantities. Their main “function” appears to be simply their own self-replication, rather than any benefit to the host, or even any direct effect whatsoever on the host phenotype. For this reason, people sometimes refer to transposons as “selfish DNA”.

In addition to transposons, there is plenty of other DNA in our chromosomes that doesn't seem to code for proteins. This is sometimes called “junk DNA”. It comes in various distinct forms, such as “introns”, “satellite DNA”, and “pseudogenes”. In fact, junk DNA makes up about 97% of the human genome! Clearly despite its derogatory name, it’s worth understanding and potentially very important. However, since transposons are the most “organism-like” of junk DNA, I will only talk about them here.

There is a fair amount of genetic evidence that transposons spread “horizontally” between sexually isolated species in addition to being “vertically” passed down the evolutionary tree. However, the mechanisms of this horizontal transmission are poorly understood. One interesting fact is that certain viruses, the baculoviruses, can pick up and accomodate transposons from their hosts. They have been proposed as a possible mechanism for horizontal transmission of transposons.

The two main classes of transposons are:

Retrotransposons
and
DNA Transposons
The best book on transposons seems to be Dynamics and Evolution of Transposable Elements, by Pierre Capy, Claude Bazin, Dominique Higuet, and Thierry Langin [CBHL]. In this book, retrotransposons are called “Class I elements”, while DNA transposons are called “Class II elements”. They also discuss “Class III elements”. This seems to be a grab-bag consisting of transposons that don’t clearly fit into the other two categories. Examples include the “Foldback” elements in fruit flies, the “Tu” elements in sea urchins, and “MITEs”, or “miniature inverted repeat transposable elements”, which are found mainly in plants and fungi.
Retrotransposons
Retrotransposons copy themselves from one location in the host genome to another using an RNA intermediate, with the help of reverse transcription from RNA to DNA. This process is called “transposition”.

A rough classification of retrotransposons divides them as follows:

LTR (long terminal repeat) retrotransposons
non-LTR retrotransposons
LINEs (long interspersed nuclear elements)
SINEs (short interspersed nuclear elements)
LTR retrotransposons are 5000–9000 base pairs long and have “long terminal repeats” – repeating sequences of base pairs at both ends. Between these are the genes needed for transposition. These code for enzymes like reverse transcriptase (which copies RNA into DNA), integrase (which integrates the DNA into the host chromosome), and so on. In all these respects, LTR retrotransposons are very similar to retroviruses. The most important difference is that retrotransposons do not code for the proteins forming the viral protein coat. There seems to be some debate as to whether retrotransposons are retroviruses that have somehow lost their ability to code for a protein coat, or whether retroviruses are retrotransposons that have somehow gained this ability. Of course, the two possibilities aren't mutually exclusive!

Why do LTR retrotransposons and retroviruses have long terminal repeats? People know the answer for retroviruses. If one of these rascals creates an exact DNA copy of its RNA and sticks it into the host genome, the host won’t return the favor and create an exact RNA copy of that DNA, because it won’t copy various bits that don’t code for proteins, like the “promoter” – the bit of DNA that tells the host to create an RNA copy! To make up for this, the virus has to do some complicated tricks. Among other things, it creates duplicate copies of some of its RNA in the host DNA. As this happens over and over, long repetitive sequences build up in the host DNA: the long terminal repeats.

The precise process is pretty complicated – too complicated for me to explain here. If you're interested, you can watch a movie of how long terminal repeats get formed by retroviruses! I guess it works similarly for LTR retrotransposons, but I'm not really sure.

As the name suggests, non-LTR retrotransposons lack terminal repeats. They have been divided into LINEs and SINEs. LINEs have a characteristic adenosine-rich sequence at one end, and are generally 5000–8000 base pairs long, though truncated versions are common. They code for various enzymes such as reverse transcriptase and RNase. The genomes of higher animals and plants may have over 10,000 copies of LINEs. In fact, about 21% of the human genome consists of LINEs!

SINEs are usually shorter than 500 base pairs. The source of the enzymes needed for the mobility of SINEs is not yet known – but perhaps it is LINEs! Higher animals and plants may have over 100,000 copies of SINEs.

DNA transposons
DNA transposons mainly move using a cut-and-paste mechanism: they code for an enzyme called a “transposase” that catalyzes a process in which the transposon DNA is excised and reinserted elsewhere in the host genome. Thus RNA and reverse transcriptase plays no role in their life cycle. As far as I can tell they don’t reproduce themselves, only move around. Given this, they probably don’t deserve to be called “alive”!

Prions
Prions are small, proteinaceous infectious particles that contain no detectable nucleic acid of any form, but are transmissible among certain animals, where they cause fatal brain diseases. These particles are rod-shaped, about 165 nanometers long and about 11 nanometers in diameter, and they consist largely of a protein called PrPSc, having molecular weight 33,000–35,000. They are able to resist inactivation by boiling, acid (pH 3–7), ultraviolet radiation (254 nm), formaldehyde, and nucleases! They can be inactivated by boiling in detergents, alkali (pH > 10), autoclaving at 132 degrees centigrade for over 2 hours, and denaturing organic solvents such as phenol.

Stanley Prusiner won the Nobel prize for medicine in 1997 for his work on prions. His theory is that prions are a modified form of a protein naturally occuring in the brain (PrP), and that this modified form can arise from a cell mutation, but then spread by means of a kind of autocatalyzed chain reaction. This theory was initially very controversial, because all other self-reproducing biological entities appear to contain RNA or DNA. There are still many doubters. In the earlier literature prions are sometimes called “slow viruses”, because of their slow effect. However, no virus has ever been associated with prion diseases.

Prions have recently received a lot of publicity as the cause of “mad cow disease”, technically known as bovine spongiform encephalopathy. Starting in the mid-1980s, this disease infected thousands of cattle in England, in part because they were being fed offal containing nerve tissue from sheep infected with a prion-caused disease called “scrapie”. People got worried that eating meat from cows with bovine spongiform encephalopathy could cause a prion-induced brain disease in people. This caused an enormous uproar.

There are already a number of prion-induced brain diseases in people, such as Creutzfeldt-Jakob disease (which occurs spontaneously in about one in a million people) and kuru (transmitted by means of cannibalism among the Fore tribe in New Guinea). There are also prion-induced brain diseases in mink, cats, deer and moose.

You can get a lot of information about prions from the prion science archives. There are also a couple of online courses on virology at All the Virology on the WWW, and these include a nice lecture on prions.

Mycoplasmas
Mycoplasmas are bacteria with a very small genome and no cell wall! They are smaller than 450 nanometers in diameter. One of them, Mycoplasma pneumoniae, has been completely sequenced, it has a genome with about 800,000 base pairs, as compared to 10 million for a typical bacterium. It is thought to be responsible for both tracheobronchitis and primary atypical pneumonia, but there is a lot of controversy surrounding it. In particular, some people argue that it has connections with Gulf War Syndrome and AIDS, while others (who sound a bit nutty to me) claim it has been genetically engineered to become more virulent.

Another distinctive feature of mycoplasmas is their response to the codon UGA – that is, uracil/guanine/adenosine, a triplet of bases in their DNA. When they read this they make the amino acid tryptophan. All other bacteria use UGA as a “stop codon” – that is, a signal that a given gene has ended. In this respect mycoplasmas are like mitochondria (the “powerhouses of the cell”), which also produce tryptophan when they read UGA. Since mitochondria were once organisms on their own, which became symbiotes and eventually merged with the cells of animals and plants, could this be a clue that mycoplasmas are more closely related to mitochondria than to other bacteria?

Two good sources of information on mycoplasmas are Katherine Howard's webpage and Joel Baseman and Joseph Tully's article in the journal Emerging Infectious Diseases, entitled Mycoplasmas: sophisticated, reemerging, and burdened by their notoriety. A lot of articles on mycoplasmas are available from the Rain-Tree website.

Nanobacteria
Nanobacteria are the most mysterious of all the things described on this webpage. They might not exist at all! The idea is that they are single-celled organisms that are much smaller than other bacteria: between 50 and 200 nanometers in size.

The idea of nanobacteria appears to have been conceived by the geologist Robert Folk in 1988. Using a scanning electron microscope to examine mineral deposits in hot springs, he saw “hordes of tiny bumps and balls” and theorized that they were very small single-celled organisms. Eventually he decided that nanobacteria were very important for geology and may even form most of the earth's biomass! For more on this, read his paper Nanobacteria: surely not figments, but what under heaven are they?

In 1998, two Finnish scientists claimed to have grown nanobacteria in a culture, but others have argued that their results are flawed and that these small balls are formed by purely chemical (i.e. nonliving!) processes. So, as far as I can tell, the existence of nanobacteria remains hotly disputed. A great source of information on this puzzle is the nanobiology webpage of the journal naturalSCIENCE.

References
Here are some good books and articles to read about this stuff:

[B] Plasmids, by Paul Broda, W.H. Freeman, San Francisco, 1979.

[CBHL] Dynamics and Evolution of Transposable Elements, by Pierre Capy, Claude Bazin, Dominique Higuet, and Thierry Langin, Landes Bioscience, 1998.

[CHV] Retroviruses, John M. Coffin, Stephen H. Hughes, and Harold E. Varmus, Cold Spring Harbor Laboratory Press, Plainview, New York, 1997.

[CT] Principles of Bacteriology, Virology and Immunity, vol. 4: Virology, edited by L. H. Collier and M. C. Timbury, 8th edition, Decker, 1990.

[Da] The Fifth Miracle, Paul Davies, Simon and Schuster, New York, 1999, pp. 127–128.

[Di] The Viroids, edited by Theodore Otto Diener, Academic Press, 1985.

[EO] 30 years later – a new approach to Sol Spiegelman’s and Leslie Orgel's in vitro evolutionary studies: dedicated to Leslie Orgel on the occasion of his 70th birthday, M. Eigen and F. Oehlenschlager, Orig. Life Evol. Biosph. 5–6 (1997), 437–457.

[E] Plasmids of Eukaryotes: Fundamental and Applications, K. Esser et al, Springer-Verlag, New York, 1986.

[F] Virology, 2 volumes, edited by Bernard N. Fields, David M. Knipe and Peter M. Howley, Lippincott-Raven Publishers, 3rd edition, 1996.

[H] Bacterial Plasmids, Kimber Hardy, American Society for Microbiology, Washington D.C., 1986.

[LA] Beneficial role of human endogenous retroviruses: facts and hypotheses, E. Larsson and G. Andersson, Scand. J. Immunol. 48 (1998), 329–338.

[MM] Subviral Pathogens of Plants and Animals: Viroids and Prions, edited by K. Maramorosch and J. J. McKelvey, Jr.., Plenum Press, 1987.

[Ma1] Viroids and Satellites: Molecular Parasites at the Frontier of Life, edited by Karl Maramarosch, CRC Press, 1991.

[Ma2] The Atlas of Insect and Plant Viruses: Including Mycoplasmaviruses and Viroids, edited by Karl Maramorosch, Academic Press, 1977.

[Mo] The Evolutionary Biology of Viruses, edited by Stephen S. Morse, Raven Press, 1994.

[Re] Virus Taxonomy: the Classification and Nomenclature of Viruses, Seventh Report of the International Committee on Taxonomy of Viruses, edited by M. H. V. van Regenmorel et al., Academic Press, 2000.

[Ro] Plant Infectious Agents: Viruses, Viroids, Virusoids, and Satellites, edited by Hugh D. Robertson et al., Cold Spring Harbor Laboratory, Plainview, New York, 1983.

[T] Escape from prisoners dilemma in RNA phage 6, Paul E. Turner and L. Chao, American Naturalist 161 (2003), 497–505.

[V] On viruses, sex, and motherhood, Luis P. Villareal, J. Virology 71 (1997), 859–865.

baez@math.ucr.edu © 2005 John Baez

 

Subcellular Life Forms

John Baez

August 12, 2017

Also available in PDFPostscript and LaTeX, thanks to Stephen Mulraney. Alas, I have drastically updated the 1998 version of this webpage, but these revisions are not yet included in the PDF, Postscript and LaTeX files.

I like biology, but as a mathematician I am drawn to the elegance of the very simplest forms of life: the subcellular life forms. They are so simple, in fact, that even calling them “alive” can be controversial. They lack many of the usual features of life. They don’t have cell walls, most of them don’t metabolize, and they are all parasitic, depending on other organisms for their ability to reproduce! Some of them even have no genetic code! Many of them cause diseases, but others are crucial to the well-being of their host, and many are so well integrated with their host that it becomes difficult to decide whether they are part of the host or a separate entity.

Indeed, besides my love of elegance and my morbid fascination with parasites, the main reason subcellular life forms appeal to me is that they challenge our naive notion of organisms as entities with clear, well-defined boundaries. It’s clear by now that life doesn't respect this simple picture. Whenever a pattern of any sort, however abstract, is able to replicate itself, it does! Typically these patterns overlap and interact in subtle ways, so one can't easily say where one ends and the other begins.

These are the main kinds of subcellular life forms that I know about so far:

I'll say a little about each kind.

I am just beginning to learn about

and which are not exactly “subcellular”, but still interesting – and controversial!

it’s hard to classify these life forms, since they don’t all have “species” in the usual sense, and they don’t fit into the standard “kingdoms” of cellular life – a classification scheme which is itself somewhat outdated. In my first attempts to understand the taxonomy of subcellular life, I was greatly aided by Diener and Prusiner's 1987 article The recognition of subviral pathogens [MM]. But in subsequent decades knowledge of these creatures has grown vastly, thanks to work on biotechnology. Now there's even a special committee devoted to their classification, called the International Committee on Taxonomy of Viruses (though they also tackle some other subcellular life forms). They even have a nice online database explaining their classification scheme.

But beware! People still argue about the correct classification of subcellular life forms. That's part of what's interesting about them: they really stretch our ideas in biology to the breaking point.

One thing to keep in mind: these life forms are small. Remember that DNA is a double helix containing information in the form of AT and CG “base pairs” – that is, paired molecules of adenine and thymine, or cytosine and guanine. Single-stranded RNA is a single helix containing information in the form of A, U, C, and G “bases” – molecules of adenine, uracil, cytosine and guanine. The human genome is made of DNA and contains about 5 billion base pairs. The genome of a bacterium is also made of DNA but has less than 10 million bases. The potato spindle tuber viroid, on the other hand, is nothing but a circular loop of RNA consisting of 359 bases! Small, simple – but effective!

The potato spindle tuber viroid is the smallest naturally self-replicating bit of RNA. “Spiegelman’s Monster” is even smaller – it consists of just 220 bases! But this entity survives only under artificial conditions. The story of this monster is fascinating. Here is Paul Davies' [Da] account of it:

The Qb virus doesn't need anything as complicated as a cell in order to replicate: a test tube full of suitable chemicals is enough. The experiment, conducted by Sol Spiegelman of the University of Illinois, consisted of introducing the viral RNA into a medium containing the RNA's own replication enzyme, plus a supply of raw materials and some salts, and incubating the mixture. When Spiegelman did this, the system obligingly replicated the strands of naked RNA. Spiegelman then extracted some of the freshly synthesized RNA, put it in a separate nutrient solution, and let it multiply. He then decanted some of that RNA into yet another solution, and so on, in a series of steps.

The effect of allowing unrestricted replication was that the RNA that multiplied fastest won out, and got passed on to the “next generation” in the series. The decanting operation therefore replaced, in a highly accelerated way, the basic competition process of Darwinian evolution, acting directly on the RNA. In this respect it resembled an RNA world.

Spiegelman’s results were spectacular. As anticipated, copying errors occurred during replication. Relieved of the responsibility of working for a living and the need to manufacture protein coats, the spoon-fed RNA strands began to slim down, shedding parts of the genome that were no longer required and merely proved to be an encumbrance. The RNA molecules that could replicate the fastest simply out-multiplied the competition. After seventy-four generations, what started out as an RNA strand with 4,500 nucleotide bases ended up as a dwarf genome with only 220 bases. This raw replicator with no frills attached could replicate very fast. It was dubbed Spiegelman’s monster.

Incredible though Spiegelman’s results were, an even bigger surprise lay in store. In 1974, Manfred Eigen and his colleagues also experimented with a chemical broth containing Qb replication enzyme and salts, and an energized form of the four bases that make up the building blocks of RNA. They tried varying the quantity of viral RNA initially added to the mixture. As the amount of input RNA was progressively reduced, the experimenters found that, with little competition, it enjoyed untrammeled exponential growth. Even a single RNA molecule added to the broth was enough to trigger a population explosion. But then something truly amazing was discovered. Replicating strands of RNA were still produced even when not a single molecule of viral RNA was added! To return to my architectural analogy, it was rather like throwing a pile of bricks into a giant mixer and producing, if not a house, then at least a garage. At first Eigen found the results hard to believe, and checked to see whether accidental contamination had occurred. Soon the experimenters convinced themselves that they were witnessing for the first time the spontaneous synthesis of RNA strands form their basic building blocks. Analysis revealed that under some experimental conditions the created RNA resembled Spiegelman’s monster.

In 1997, further experiments by Eigen and Oehlenschlager [EO] showed that Spiegelman’s monster eventually evolves (under the same unnatural conditions) to two kinds of RNA, one consisting of 54 bases and one consisting of only 48!

One thing this shows is that viruses will always evolve towards becoming smaller if it helps them reproduce faster. Experiments by Turner [T] have shown that viruses will gladly “cheat” and drop some of their genes if there are enough other viruses of the same sort around doing the work these genes allow. This leads to some interesting problems in game theory, related to the so-called Prisoner's Dilemma. This tendency of viruses to shrink to the bare minimum may explain how satellites came into existence.

By the way: please email me if you find mistakes in this webpage, or if you know any more fascinating facts about subcellular life forms – especially if you know kinds that aren't on this list! It will take me a long time to reply, but I eventually will. I would like to thank Daniele Focosi for doing this, and urge everyone to look at his webpage on the physiology of subcellular life forms. I also thank Axel Boldt.

 


 

Viruses

Diener and Prusiner define a virus to be a “small infectious pathogen composed of one or more nucleic acid molecules usually surrounded by a protein coat.” They typically reproduce by latching onto the wall of a cell and inserting their genetic material – i.e., the nucleic acids – into the cell. This genetic material then uses the cell's machinery to make more copies of the virus. Typically, these copies overrun the cell until it bursts. However, the actual life cycle of a virus is often more complicated than this thumbnail sketch! Viruses use a large number of sneaky tricks to overcome the defense mechanisms of the cell.

Apart from their intrinsic interest, viruses are important because they cause many diseases among humans, such as:

as well as diseases of domesticated animals and plants. For a detailed tour, try The Big Picture Book of Viruses, available online. For even more information, try the chapter on virology prepared by Margaret and Richard Hunt as part of a wonderful online textbook called Microbiology and Immunology.

There is by now a standard taxonomy of viruses [F][CT] [Ma2][Re]. Here, however, I will content myself with a rough classification of viruses into following 3 sorts:

and

 

DNA viruses

The genome of a DNA virus is a single molecule of DNA, either linear or circular. Outside the host cell, this DNA is usually surrounded by a protein coat. There are 5 known families of DNA viruses affecting humans. The size and structure of the DNA viruses varies widely, from small ones with only 5,000 base pairs to the large brick-shaped or ovoid pox viruses, which have a lipid coating and whose DNA has between 120,000 and 360,000 base pairs.

One can broadly classify the DNA viruses into two kinds:

If you click on the options above you'll see that most known DNA viruses are double-stranded, including all the DNA viruses that affect humans.

 

RNA viruses

The genome of an RNA virus is usually a single molecule of RNA, either linear or circular, but some contain up to a dozen molecules of RNA. Outside the host cell, this RNA is protected by a protein coat. Most viruses are RNA viruses. There are 13 known families of RNA viruses affecting humans. RNA viruses range widely in morphology and size, with their genome containing anywhere from 1,700 to 60,000 nucleotides.

The smallest RNA virus, the hepatitis delta agent (HDV), is quite different from all the rest. With only about 1,700 nucleotides, its genome is much smaller than that of any other virus. Like a virusoid, it’s a circular loop of RNA that can only reproduce in cells infected by a helper virus, the hepatitis B virus. But unlike a virusoid, it codes for its own protein coat. Its genome is also much bigger than those of virusoids, which have only about 350 nucleotides. In these ways it’s more like a viroid. However, viroids only infect plants!

One can broadly classify RNA viruses into:

A “positive-sense” RNA virus consists of single-stranded RNA that functions directly as messenger RNA in the host cell, so that ribosomes in the host cell synthesize various proteins needed by the virus when encountering this RNA. A “negative-sense” RNA virus consists of single-stranded RNA that does not function as messenger RNA, since it contains the complementary base pairs. Negative-sense RNA viruses carry enzymes with them into the host cell to synthesize messenger RNA from the RNA in the virus. “Double-stranded” RNA viruses have both positive-sense and negative-sense strands. For some reason these are more likely to consist of several separate pieces of RNA. If you click on the options listed above, you'll see examples of these different kinds of RNA viruses.

 

Reverse transcribing viruses

Reverse transcribing viruses behave quite differently from the other viruses described above. There are two main kinds of reverse transcribing viruses:

If you click on these options you'll see examples of both kinds.

 

RNA reverse transcribing viruses are usually called retroviruses”. They have a single-stranded RNA genome. They infect animals, and when they get inside the cell's nucleus, they copy themselves into the DNA of the host cell using reverse transcriptase. In the process they often cause tumors, presumably by damaging the host's DNA.

Retroviruses are important in genetic engineering because they raised for the first time the possibility that RNA could be transcribed into DNA, rather than the reverse. In fact, some of them are currently being deliberately used by scientists to add new genes to mammalian cells.

Retroviruses are also important because AIDS is caused by a retrovirus: the human immunodeficiency virus (HIV). This is part of why AIDS is so difficult to treat. Most usual ways of killing viruses have no effect on retroviruses when they are latent in the DNA of the host cell.

From an evolutionary viewpoint, retroviruses are fascinating because they blur the very distinction between host and parasite. Their genome often contains genetic information derived from the host DNA. And once they are integrated into the DNA of the host cell, they may take a long time to reemerge. In fact, so-called “endogenous retroviruses” can be passed down from generation to generation, indistinguishable from any other cellular gene, and evolving along with their hosts, perhaps even from species to species! It has been estimated that up to 1% of the human genome consists of endogenous retroviruses! Furthemore, not every endogenous retrovirus causes a noticeable disease. Some may even help their hosts [LA][V].

It gets even spookier when we notice that once an endogenous retrovirus lost the genes that code for its protein coat, it would become indistinguishable from an LTR retrotransposon - one of the many kinds of “junk DNA” cluttering up our chromosomes. Just how much of us is made of retroviruses? it’s hard to be sure.

So much for retroviruses… what about DNA reverse transcribing viruses? These have a DNA genome, and instead of reverse transcriptase copying the RNA of the free-floating virus to the DNA of the host, they work the other way around. When they've infected the host cell, there is a lot of RNA floating around; they use reverse transcriptase to package themselves as DNA when they leave the cell!

There aren't many DNA reverse transcribing viruses. Most of them are relatives of the hepatitis B virus (HBV). This virus attacks liver cells, and can cause tumors. Unlike a typical DNA virus, the hepatitis B virus consists of both single-stranded and double-stranded DNA. it’s also smaller than any DNA virus: its nucleotide consists of only about 2,400 base pairs.

I wonder why the viruses affecting the liver are so strange and diverse. The hepatitis B virus is quite unusual, and I've already mentioned its even more bizarre symbiote (or parasite): the hepatitis delta agent (HDV), which is the smallest RNA virus, and different from all the rest. There are also four other forms of hepatitis: positive-sense RNA viruses called HAVHCVHEV, and HGV. None of these are in the same family! Apparently all they have in common is that they attack the liver.

 


 

Viroids

A viroid is defined to be a “small infectious pathogen composed entirely of a low molecular weight RNA molecule”. Thus, unlike a virus, a viroid has no protein coat. It is nothing but a single-stranded circular loop of RNA! Most viroids consist of about 250 to 375 nucleotides, much smaller than a typical virus. Also, viroids don’t function as messenger RNAs, so they don’t make the cell synthesize enzymes: they rely completely on pre-existing enzymes in the host for their reproduction.

Most known viroids cause diseases in plants. The first viroid was discovered in 1971, by Diener. it’s called the potato spindle tuber virus (PSTV), since it causes a disease that makes potatos abnormally long and sometimes cracked. At the time, Diener's isolation of the viroid causing this disease met with some skepticism, since it was so much smaller than any known virus. By 1991, however, at least 15 plant diseases had been traced to viroids. There are also 2 viroids known, the hop latent viroid (HLV) and a viroid living in grapevines, that cause no known symptoms! This raises the fascinating possibility that there could be more such viroids lurking around.

The complete molecular structure of many viroids has been worked out, which has allowed a classification of viroids on the basis of their RNA sequences. Roughly speaking, there are a large family of viroids that share many features with PSTV, together with one viroid that seems very different: the avocado sunblotch viroid (ASBV). McInnes and Simons have proposed a further classification of the PSTV-type viroids into three kinds [Ma1].

It is clear from these RNA sequences that viroids are not “degenerate viruses”, as had once been thought. They are quite different from any known viruses. One interesting theory is that they arose from RNA that escaped from cell nuclei.

it’s also interesting that all viroid diseases have been detected in the 20th century, some quite recently – in contrast to diseases caused by viruses. Also, many viroid diseases have been spreading after their discovery, often due to human activity. A fascinating example is the coconut cadang-cadang viroid (CCCV), a disease of coconuts which has been spreading throughout the Phillipines. On the island of Luzon, a puzzling feature of this disease was that it only affected crops owned by speakers of Bicalano, while adjacent crops owned by speakers of Tagalog went unharmed! Eventually people realized that the viroids were spread by workers cutting the palms. Tagalog owners prefer to hire Tagalog workers, while Bicalanos hire Bicalanos, some of whom came from an area where the disease was prevalent. (See the article by Maramarosch entitled The cadang-cadang viroid disease of palms [Di].)

Because of this sort of epidemiology, Diener has suggested that viroids may be latent to their native host plants (like HLV), becoming pathogenic only when transferred to other species thanks to agriculture. Indeed, the viroid causing tomato “planta macho” disease in Mexico, TPMV, has also been found in wild plants there. Also, an avocado plant will sometimes seem to “recover” from ASBV by sending up a new shoot. This new shoot is still infected with the viroid, but it shows no symptoms other than reduced fruit yield. Descendants of such a “recovered” tree are also infected with the viroid, and also symptomless, except for reduced fruit yield. Thus the avocado appears able to “come to terms” with the viroid in some way. Personally, I'd like to raise this possibility: that some viroids actually play a beneficial role in their native host plants! This may seem surprising, but when we compare the behavior of plasmids, it may seem less so.

 


 

Satellites

A satellite is a “sub-viral agent composed of nucleic acid molecules that depends for its reproduction on co-infection of a host cell with a helper virus”. In other words, just as a planet can have a moon orbiting it, a virus can have a satellite orbiting it!

There are various kinds of satellites:

A “satellite virus” is a satellite whose genome codes for the protein coat in which it is encapsidated. All known satellite viruses have a genome made of single-stranded RNA. There are only five known kinds. A good example is the tobacco mosaic satellite virus, which goes along with the well-known tobacco mosaic virus (TMV).

A “satellite nucleic acid” is a satellite whose genome does not code for a protein coat; instead, it hides in the protein coat of its virus helper! A satellite nucleic acid can consist of either DNA or RNA. All known satellite DNAs are single-stranded, but satellite RNAs can be single- or double-stranded.

Single-stranded satellite RNAs are fascinating because they include the very smallest forms of life known – the virusoids! These are circular loops of single-stranded RNA containing about 350 nucleotides. They can only reproduce in cells that have been infected by their helper virus, because they use some of the RNA of the helper virus to reproduce. The helper virus is typically an RNA virus which causes a disease of plants and consists of about 4500 nucleotides.

One might be tempted to say that a virusoid is a parasite of its helper virus. But it’s not always so simple. Sometimes the helper virus is unable to reproduce unless the virusoid is present! Then we have symbiosis rather than parasitism.

The first virusoids were discovered in the early 1980s in Australia, associated with viruses causing diseases such as velvet tobacco mottle (VTMoV), solanum nodiflorum mottle (SNMV), lucerne transient streak (LTSV), and subterranean clover mottle (SCMoV).

An interesting theory about the origin of virusoids is that in plants infected with both viruses and viroids, the viroids got encapsidated in the viruses and later lost their ability to reproduce independently.

An easy way to learn more about viroids and satellites is to read the online course notes by the plant pathologist Zhongguo Xiong. In fact, if you like subcellular life forms, his whole course on plant virology is worth reading!

 


 

Plasmids

A plasmid is a “small autonomously replicating circular molecule of DNA that is devoid of protein and not essential for the survival of its host”. Plasmids range in size greatly, from about 4350 to 240,000 base pairs. Most known plasmids infect bacteria, but some infect plant and animal cells. They often copy themselves into the DNA of the host cell, and many carry genetic traits from one cell to another. Most plasmids keep a limit on the number of copies of themselves they keep in each host – the so-called “copy number”, which ranges from 1 to about 40. Many plasmids are “conjugative”. This means they can transfer copies of themselves from one host to another by forcing the host to undergo “conjugation” – a form of sex in which genetic material is exchanged between bacteria.

People tend not to speak of plasmids as “life forms” quite as often as they do with viruses. In part this may be because plasmids are sometimes beneficial to their host cells, rather than pathogenic.

However, is difficult for me to resist the impression that plasmids are just as “alive” as viruses. Indeed, some viruses become plasmids when parts of them are missing! For example, the “lambda bacteriophage” is a virus that infects the intestinal bacterium E. coli, but “lambda dv particles”, which arise from the lambda phage simply by deleting some DNA, are plasmids. The lambda phage multiplies inside its host and then kills it by “lysis”, which destroys the cell membrane and releases lots of copies. The lambda dv particles, on the other hand, stays in the cell in a fairly stable number of copies and does not kill its host. The difference is that while the lambda dv particles contain genes for replication, they lack genes for lysis and the protein coat.

If we think of plasmids as life forms, we must admit that they are very successful. Many plasmids spread so thoroughly in cultures of bacteria that less than one cell in 100,000 lacks a copy! Some kinds of plasmids contain genes that help make sure copies are efficiently passed on to both daughter cells when the host cell divides. F plasmids have a particularly clever mechanism – they temporarily inhibit cell division when they have not yet replicated inside the host!

Plasmids are diverse and very interesting. Some important kinds are:

and

While they don’t quite fit under this heading, I can't resist also mentioning

and

These are man-made entities based on plasmids, used in biotechnology. Are they alive? You judge.

Some good books on plasmids include Plasmids by Paul Broda [B]Bacterial Plasmids by Kimber Hardy [H], and Plasmids of Eukaryotes: Fundamentals and Applications by K. Esser et al [E].

 

R Plasmids

R plasmids were first discovered in Japan in 1957. In Japan, dysentery was treated with sulphonamide until about 1950. Then, more and more strains of the bacteria causing dysentery became resistant to this antibiotic, rapidly rendering it ineffective. Doctors then began using tetracycline, streptomycin and chloramphenicol. By 1957, 2% of the bacteria causing dysentery were resistant to one or more of these drugs, and by 1960, 13% were resistant. It turned out that R plasmids were the culprit!

R plasmids contain genes that give their bacterial hosts resistance to antibiotics as well as to poisonous metal ions such as arsenic, silver, copper, mercury, lead, zinc and so on. Because many R plasmids are conjugative, this resistance can spread from one bacterium to another. Because they can live in more than one species of bacteria, R plasmids can also spread resistance between bacteria of different species!

Spread of resistance to antibiotics is now a major problem in medicine. Drugs which were used for many years to control bacterial diseases are now becoming helpless against new resistant strains. The problem has been made worse by the tendency for doctors and veterinarians to use antibiotics when they aren't strictly necessary, for example as part of livestock food. As a result an environment is created where bacteria with resistance have a great competitive advantage, so they spread rapidly.

It has also recently been found that weeds growing near crops that were genetically engineered to resist herbicides can acquire this trait. I'm not sure, but I suspect that this happens via plasmids as well.

R plasmids make it clear that the idea of evolution as a battle between species with separately evolving genomes is a great oversimplification. Instead, genetic communication and cooperation between different species can be very important.

 

F Plasmids

F plasmids live in the bacterium E. coli and were discovered in the 1920s. An F plasmid contains genes that make the cell membrane of its host form long tubes. These tubes, called “sex pili”, attach themselves to other E. coli and puncture their cell membranes. The F plasmid then duplicates and a copy passes from the original host to the new host. A clever system has evolved to ensure that the sex pili of a given bacterium never attach to itself.

F plasmids give their hosts no known traits besides these sex pili. The evolutionary origins of sex are much debated these days; we see here the fascinating possibility that sex can originate as a kind of disease whose sole function is to spread a parasite!

 

Colicin Plasmids

Colicin plasmids contain genes that give their host bacterium a certain small probability of bursting open and releasing chemicals called “colicins”. These chemicals kill other bacteria by rendering their cell membranes permeable to important ions. There are many strains of colicin plasmid. Each one confers immunity only to the particular sort of colicin it produces. Different strains of colicin plasmid are “incompatible”, meaning that a given strain bacterium cannot stably contain both.

In short, different strains of colicin plasmid compete with each other using the resources of their hosts. A colicin plasmid will confer an advantage to its host bacteria if the other strains of bacteria nearby do not have a colicin plasmid. However, when there are many different strains of colicin plasmid present, all strains of host bacteria suffer. Thus there is a certain similarity between colicin plasmids and “protection rackets” run by Mafia-like gangs.

Colicin plasmids are not the only sort of plasmids that exhibit incompatibility. Similar plasmids tend to be incompatible with each other, while drastically different plasmids are usually compatible. One theory is that incompatible plasmids use the same mechanisms to maintain their copy number. In a cell containing two incompatible sorts of plasmid, their reproduction is blocked until the total number of copies of the two together drops to the copy number of each one. This is an unstable situation, especially for plasmids with a low copy number, so eventually descendants of the host cell contain only one or the other plasmid.

 

Virulence Plasmids

Virulence plasmids contain genes that make their bacterial hosts more virulent to their hosts. A familiar example involves the bacterium E. coli, which inhabits the human large intestine. Certain strains of E. coli contain plasmids whose genes make the E. coli synthesize toxins that cause diarrhea. These “enterotoxigenic strains” of E. coli are probably an important cause of diarrhea among travellers. More seriously, in developing countries, diarrhea is one of the principal causes of death among those under five.

“Vibrio cholerae”, the cause of cholera, is a bacterium whose genes code for a diarrhea-causing toxin. The DNA of these genes is closely related to the DNA of certain virulence plasmids infecting E. coli – so closely that there is almost certainly a common ancestor. For example, Vibrio cholerae could have evolved from an earlier bacterium by permanently integrating the DNA from a virulence plasmid into its genome.

Strains of bacteria and viruses often become less virulent as they coevolve with their hosts. Thus one may wonder what evolutionary advantage a virulence plasmid could confer to the bacteria containing it. In the case of bacteria causing diarrhea, there is an obvious possibility: diarrhea can serve as a mechanism for spreading the bacteria – and their plasmids – that cause it!

 

Metabolic Plasmids

Metabolic plasmids contain genes that let their bacterial hosts metabolize or degrade otherwise indigestible or toxic chemicals. For example, the bacterium Pseudomonas putida is able to grow on a wide range of organic compounds that are toxic to most bacteria, including toluene, octane, camphor, napthalene and nicotinic acid! It does this with the help of genes contained by metabolic plasmids called TOL, OCT, CAM, NAH and NIC plasmids.

it’s worth noting that some of these chemicals are secreted by plants as part of a defense against bacteria. Thus we probably have a kind of natural chemical arms race going on here. Other metabolic plasmids allow bacteria to degrade herbicides like 2,4-D, as well as certain detergents! People are investigating the use of such plasmids to help biodegrade pollution.

 

 

Tumor-Causing Plasmids

“Crown gall” is a cancer of plants caused by a bacterium known as Agrobacterium tumefaciens. But actually, the disease is caused by a plasmid having this bacterium as its host! When the plasmid passes from the bacterium to the cells of infected fruit trees, some of the genes contained in the plasmid cause tumors. Do these tumors help spread the bacteria to other trees?

 

 

Cryptic Plasmids

Cryptic plasmids are plasmids that have no known effect on their hosts. How much of this is our ignorance, and to what extent is being truly “cryptic” a successful strategy?

 

Cosmids

Cosmids are man-made circular loops of DNA containing plasmid DNA together with an arbitrary sequence of up to 45,000 base pairs of DNA. They are constructed by recombinant DNA techniques and then packaged in lambda phage protein coats. They are used to transfer genes to bacteria.

The lambda phage is a virus that specializes in invading bacteria such as E. coli. In nature, its protein coat latches onto the bacterial cell membrane and injects the phage DNA into the bacterium. Biotechnologists have taken advantage of this by using the lambda phage protein coat to inject a cosmid into the bacterium! Once inside, the cosmid replicates like a plasmid and, like a plasmid, integrates its DNA into the genome of the bacterium.

 

Phasmids

Phasmids are man-made linear DNA molecules whose ends are sequences taken from the lambda phage, while the middle is a sequence taken from a plasmid, together with a sequence of whatever DNA one wants. Like cosmids, they are constructed by recombinant DNA techniques and packaged in lambda phage protein coats, and used to transfer genes to bacteria. However, both the lambda phage and plasmid replication functions are intact. In particular, they contain the lambda phage genes for “lysis”, the process whereby a virus dissolves the cell membrane of its host. Depending on the conditions, the phasmid can act either like a phage or a plasmid – hence its name.

 


 

Transposons

Transposons, or “transposable elements”, are sequences of DNA that move within their host's genome from one position to another. They were first discovered in the 1940s by Barbara McClintock, who later won the Nobel prize for this work. They exist in all known organisms, often in large quantities. Their main “function” appears to be simply their own self-replication, rather than any benefit to the host, or even any direct effect whatsoever on the host phenotype. For this reason, people sometimes refer to transposons as “selfish DNA”.

In addition to transposons, there is plenty of other DNA in our chromosomes that doesn't seem to code for proteins. This is sometimes called “junk DNA”. It comes in various distinct forms, such as “introns”, “satellite DNA”, and “pseudogenes”. In fact, junk DNA makes up about 97% of the human genome! Clearly despite its derogatory name, it’s worth understanding and potentially very important. However, since transposons are the most “organism-like” of junk DNA, I will only talk about them here.

There is a fair amount of genetic evidence that transposons spread “horizontally” between sexually isolated species in addition to being “vertically” passed down the evolutionary tree. However, the mechanisms of this horizontal transmission are poorly understood. One interesting fact is that certain viruses, the baculoviruses, can pick up and accomodate transposons from their hosts. They have been proposed as a possible mechanism for horizontal transmission of transposons.

The two main classes of transposons are:

and The best book on transposons seems to be Dynamics and Evolution of Transposable Elements, by Pierre Capy, Claude Bazin, Dominique Higuet, and Thierry Langin [CBHL]. In this book, retrotransposons are called “Class I elements”, while DNA transposons are called “Class II elements”. They also discuss “Class III elements”. This seems to be a grab-bag consisting of transposons that don’t clearly fit into the other two categories. Examples include the “Foldback” elements in fruit flies, the “Tu” elements in sea urchins, and “MITEs”, or “miniature inverted repeat transposable elements”, which are found mainly in plants and fungi.

 

Retrotransposons

Retrotransposons copy themselves from one location in the host genome to another using an RNA intermediate, with the help of reverse transcription from RNA to DNA. This process is called “transposition”.

A rough classification of retrotransposons divides them as follows:

LTR retrotransposons are 5000–9000 base pairs long and have “long terminal repeats” – repeating sequences of base pairs at both ends. Between these are the genes needed for transposition. These code for enzymes like reverse transcriptase (which copies RNA into DNA), integrase (which integrates the DNA into the host chromosome), and so on. In all these respects, LTR retrotransposons are very similar to retroviruses. The most important difference is that retrotransposons do not code for the proteins forming the viral protein coat. There seems to be some debate as to whether retrotransposons are retroviruses that have somehow lost their ability to code for a protein coat, or whether retroviruses are retrotransposons that have somehow gained this ability. Of course, the two possibilities aren't mutually exclusive!

Why do LTR retrotransposons and retroviruses have long terminal repeats? People know the answer for retroviruses. If one of these rascals creates an exact DNA copy of its RNA and sticks it into the host genome, the host won’t return the favor and create an exact RNA copy of that DNA, because it won’t copy various bits that don’t code for proteins, like the “promoter” – the bit of DNA that tells the host to create an RNA copy! To make up for this, the virus has to do some complicated tricks. Among other things, it creates duplicate copies of some of its RNA in the host DNA. As this happens over and over, long repetitive sequences build up in the host DNA: the long terminal repeats.

The precise process is pretty complicated – too complicated for me to explain here. If you're interested, you can watch a movie of how long terminal repeats get formed by retroviruses! I guess it works similarly for LTR retrotransposons, but I'm not really sure.

As the name suggests, non-LTR retrotransposons lack terminal repeats. They have been divided into LINEs and SINEs. LINEs have a characteristic adenosine-rich sequence at one end, and are generally 5000–8000 base pairs long, though truncated versions are common. They code for various enzymes such as reverse transcriptase and RNase. The genomes of higher animals and plants may have over 10,000 copies of LINEs. In fact, about 21% of the human genome consists of LINEs!

SINEs are usually shorter than 500 base pairs. The source of the enzymes needed for the mobility of SINEs is not yet known – but perhaps it is LINEs! Higher animals and plants may have over 100,000 copies of SINEs.

 

DNA transposons

DNA transposons mainly move using a cut-and-paste mechanism: they code for an enzyme called a “transposase” that catalyzes a process in which the transposon DNA is excised and reinserted elsewhere in the host genome. Thus RNA and reverse transcriptase plays no role in their life cycle. As far as I can tell they don’t reproduce themselves, only move around. Given this, they probably don’t deserve to be called “alive”!

 


 

Prions

Prions are small, proteinaceous infectious particles that contain no detectable nucleic acid of any form, but are transmissible among certain animals, where they cause fatal brain diseases. These particles are rod-shaped, about 165 nanometers long and about 11 nanometers in diameter, and they consist largely of a protein called PrPSc, having molecular weight 33,000–35,000. They are able to resist inactivation by boiling, acid (pH 3–7), ultraviolet radiation (254 nm), formaldehyde, and nucleases! They can be inactivated by boiling in detergents, alkali (pH > 10), autoclaving at 132 degrees centigrade for over 2 hours, and denaturing organic solvents such as phenol.

Stanley Prusiner won the Nobel prize for medicine in 1997 for his work on prions. His theory is that prions are a modified form of a protein naturally occuring in the brain (PrP), and that this modified form can arise from a cell mutation, but then spread by means of a kind of autocatalyzed chain reaction. This theory was initially very controversial, because all other self-reproducing biological entities appear to contain RNA or DNA. There are still many doubters. In the earlier literature prions are sometimes called “slow viruses”, because of their slow effect. However, no virus has ever been associated with prion diseases.

Prions have recently received a lot of publicity as the cause of “mad cow disease”, technically known as bovine spongiform encephalopathy. Starting in the mid-1980s, this disease infected thousands of cattle in England, in part because they were being fed offal containing nerve tissue from sheep infected with a prion-caused disease called “scrapie”. People got worried that eating meat from cows with bovine spongiform encephalopathy could cause a prion-induced brain disease in people. This caused an enormous uproar.

There are already a number of prion-induced brain diseases in people, such as Creutzfeldt-Jakob disease (which occurs spontaneously in about one in a million people) and kuru (transmitted by means of cannibalism among the Fore tribe in New Guinea). There are also prion-induced brain diseases in mink, cats, deer and moose.

You can get a lot of information about prions from the prion science archives. There are also a couple of online courses on virology at All the Virology on the WWW, and these include a nice lecture on prions.

 


 

Mycoplasmas

Mycoplasmas are bacteria with a very small genome and no cell wall! They are smaller than 450 nanometers in diameter. One of them, Mycoplasma pneumoniae, has been completely sequenced, it has a genome with about 800,000 base pairs, as compared to 10 million for a typical bacterium. It is thought to be responsible for both tracheobronchitis and primary atypical pneumonia, but there is a lot of controversy surrounding it. In particular, some people argue that it has connections with Gulf War Syndrome and AIDS, while others (who sound a bit nutty to me) claim it has been genetically engineered to become more virulent.

Another distinctive feature of mycoplasmas is their response to the codon UGA – that is, uracil/guanine/adenosine, a triplet of bases in their DNA. When they read this they make the amino acid tryptophan. All other bacteria use UGA as a “stop codon” – that is, a signal that a given gene has ended. In this respect mycoplasmas are like mitochondria (the “powerhouses of the cell”), which also produce tryptophan when they read UGA. Since mitochondria were once organisms on their own, which became symbiotes and eventually merged with the cells of animals and plants, could this be a clue that mycoplasmas are more closely related to mitochondria than to other bacteria?

Two good sources of information on mycoplasmas are Katherine Howard's webpage and Joel Baseman and Joseph Tully's article in the journal Emerging Infectious Diseases, entitled Mycoplasmas: sophisticated, reemerging, and burdened by their notoriety. A lot of articles on mycoplasmas are available from the Rain-Tree website.

 


 

Nanobacteria

Nanobacteria are the most mysterious of all the things described on this webpage. They might not exist at all! The idea is that they are single-celled organisms that are much smaller than other bacteria: between 50 and 200 nanometers in size.

The idea of nanobacteria appears to have been conceived by the geologist Robert Folk in 1988. Using a scanning electron microscope to examine mineral deposits in hot springs, he saw “hordes of tiny bumps and balls” and theorized that they were very small single-celled organisms. Eventually he decided that nanobacteria were very important for geology and may even form most of the earth's biomass! For more on this, read his paper Nanobacteria: surely not figments, but what under heaven are they?

In 1998, two Finnish scientists claimed to have grown nanobacteria in a culture, but others have argued that their results are flawed and that these small balls are formed by purely chemical (i.e. nonliving!) processes. So, as far as I can tell, the existence of nanobacteria remains hotly disputed. A great source of information on this puzzle is the nanobiology webpage of the journal naturalSCIENCE.

 


References

Here are some good books and articles to read about this stuff:

[B] Plasmids, by Paul Broda, W.H. Freeman, San Francisco, 1979.

[CBHL] Dynamics and Evolution of Transposable Elements, by Pierre Capy, Claude Bazin, Dominique Higuet, and Thierry Langin, Landes Bioscience, 1998.

[CHV] Retroviruses, John M. Coffin, Stephen H. Hughes, and Harold E. Varmus, Cold Spring Harbor Laboratory Press, Plainview, New York, 1997.

[CT] Principles of Bacteriology, Virology and Immunity, vol. 4: Virology, edited by L. H. Collier and M. C. Timbury, 8th edition, Decker, 1990.

[Da] The Fifth Miracle, Paul Davies, Simon and Schuster, New York, 1999, pp. 127–128.

[Di] The Viroids, edited by Theodore Otto Diener, Academic Press, 1985.

[EO] 30 years later – a new approach to Sol Spiegelman’s and Leslie Orgel's in vitro evolutionary studies: dedicated to Leslie Orgel on the occasion of his 70th birthday, M. Eigen and F. Oehlenschlager, Orig. Life Evol. Biosph. 5–6 (1997), 437–457.

[E] Plasmids of Eukaryotes: Fundamental and Applications, K. Esser et al, Springer-Verlag, New York, 1986.

[F] Virology, 2 volumes, edited by Bernard N. Fields, David M. Knipe and Peter M. Howley, Lippincott-Raven Publishers, 3rd edition, 1996.

[H] Bacterial Plasmids, Kimber Hardy, American Society for Microbiology, Washington D.C., 1986.

[LA] Beneficial role of human endogenous retroviruses: facts and hypotheses, E. Larsson and G. Andersson, Scand. J. Immunol. 48 (1998), 329–338.

[MM] Subviral Pathogens of Plants and Animals: Viroids and Prions, edited by K. Maramorosch and J. J. McKelvey, Jr.., Plenum Press, 1987.

[Ma1] Viroids and Satellites: Molecular Parasites at the Frontier of Life, edited by Karl Maramarosch, CRC Press, 1991.

[Ma2] The Atlas of Insect and Plant Viruses: Including Mycoplasmaviruses and Viroids, edited by Karl Maramorosch, Academic Press, 1977.

[Mo] The Evolutionary Biology of Viruses, edited by Stephen S. Morse, Raven Press, 1994.

[Re] Virus Taxonomy: the Classification and Nomenclature of Viruses, Seventh Report of the International Committee on Taxonomy of Viruses, edited by M. H. V. van Regenmorel et al., Academic Press, 2000.

[Ro] Plant Infectious Agents: Viruses, Viroids, Virusoids, and Satellites, edited by Hugh D. Robertson et al., Cold Spring Harbor Laboratory, Plainview, New York, 1983.

[T] Escape from prisoners dilemma in RNA phage 6, Paul E. Turner and L. Chao, American Naturalist 161 (2003), 497–505.

[V] On viruses, sex, and motherhood, Luis P. Villareal, J. Virology 71 (1997), 859–865.

 


baez@math.ucr.edu © 2005 John Baez

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