SV40

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Simian virus 40
Virus classification Edit this classification
(unranked): Virus
Realm: Monodnaviria
Kingdom: Shotokuvirae
Phylum: Cossaviricota
Class: Papovaviricetes
Order: Sepolyvirales
Family: Polyomaviridae
Genus: Betapolyomavirus
Species:
Macaca mulatta polyomavirus 1
Virus:
Simian virus 40
Synonyms

simian vacuolating virus 40, SV40

SV40 is an abbreviation for simian vacuolating virus 40 or simian virus 40, a

tumors in animals, but most often persists as a latent infection. SV40 has been widely studied as a model eukaryotic virus, leading to many early discoveries in eukaryotic DNA replication[1] and transcription.[2]

Following contamination of

anti-vaccination activists, who have blamed it for multiple ills, including cancer and HIV/AIDS.[3]

Human disease

The hypothesis that SV40 might cause cancer in humans was a particularly controversial area of research, fuelled by the historical contamination of some batches of polio vaccine with SV40 in the 1950s and 1960s.[4] "Persuasive evidence now indicates that SV40 is causing infections in humans today and represents an emerging pathogen."[5] However "It appears unlikely that SV40 infection alone is sufficient to cause human malignancy..."[6]

p53 damage and carcinogenicity

It has been suggested that SV40 may act as a co-carcinogen with crocidolite asbestos to cause mesothelioma.[7][8]

Polio vaccine contamination

Main article: Vaccine contamination with SV40

Some vaccines made in the US between 1955 and 1961 were found to be contaminated with SV40, from the growth medium and from the original seed strain. Population level studies did not show extensive evidence of increase in cancer incidence as a result of exposure,[9] though SV40 has been extensively studied.[10] A thirty-five year follow-up did not find excess numbers of cancers associated with SV40.[11]

Gene therapy

Due to its high tissue tropism, biotechnology companies seek to utilize modified SV40 based vectors as a viral vector for gene therapy. In these helper dependent virus or packaging cell line assisted produced vectors the SV40 large T antigen and SV40 small T antigen are removed.[12][13][14]

Virology

SV40 consists of an

RNA synthesis. Binding to site II takes place in each cell cycle. Binding site I initiates DNA replication at the origin of replication. Early transcription gives two spliced RNAs that are both 19s. Late transcription gives both a longer 16s, which synthesizes the major viral capsid protein VP1; and the smaller 19s, which gives VP2 and VP3 through leaky scanning. All of the proteins, besides the 5% of large T, return to the nucleus because assembly of the viral particle happens there. A putative late protein VP4 has been reported to act as a viroporin facilitiating release of viral particles and resulting in cytolysis;[17][18] however the presence and role of VP4 have been disputed.[19][20]

Multiplicity reactivation

SV40 is capable of

multiplicity reactivation (MR).[21][22] MR is the process by which two or more virus genomes containing otherwise lethal damage interact within an infected cell to form a viable virus genome. Yamamato and Shimojo observed MR when SV40 virions were irradiated with UV light and allowed to undergo multiple infection of host cells.[21] Hall studied MR when SV 40 virions were exposed to the DNA crosslinking agent 4, 5', 8-trimethylpsoralen.[22] Under conditions in which only a single virus particle entered each host cell, approximately one DNA cross-link was lethal to the virus and could not be repaired. In contrast, when multiple viral genomes infected a host cell, psoralen-induced DNA cross-links were repaired; that is, MR occurred. Hall suggested that the virions with cross-linked DNA were repaired by recombinational repair.[22] Michod et al. reviewed numerous examples of MR in different viruses and suggested that MR is a common form of sexual interaction that provides the advantage of recombinational repair of genome damages.[23]

Transcription

The early

dimerization) with the AP-1 transcription factor to give a primary transcript that is 3' polyadenylated and 5' capped.[citation needed
]

Other animals

SV40 is dormant and is asymptomatic in

JC and BK polyomaviruses, producing kidney disease and sometimes a demyelinating disease similar to progressive multifocal leukoencephalopathy. In other species, particularly hamsters, SV40 causes a variety of tumors, generally sarcomas. In rats, the oncogenic SV40 large T antigen was used to establish a brain tumor model for primitive neuroectodermal tumor and medulloblastoma.[24]

The molecular mechanisms by which the virus reproduces and alters cell function were previously unknown, and research into SV40 vastly increased biologists' understanding of gene expression and the regulation of cell growth.[citation needed]

History

SV40 was first identified by Ben Sweet and

University of Ghent (Belgium).[28]

Culture and society

SV40 has become a totemic subject among

anti-vaccination activists, where its presence in contaminated vaccine is accused of being a cause of a cancer "epidemic" and of being responsible for HIV/AIDS.[3]

See also

References

  1. PMID 19101707
    .
  2. S2CID 54234674
    .
  3. ^ a b Gorski DH (9 September 2013). "Another antivaccine zombie meme: polio vaccine and SV40 and cancer, oh, my!". Science-Based Medicine.
  4. PMID 16963733
    .
  5. S2CID 10372679
    .
  6. PMID 21955238
    .
  7. PMID 16966607
    .
  8. S2CID 30590705
    .
  9. ^ "Studies Find No Evidence That Simian Virus 40 Is Related To Human Cancer". Science Daily (Press release). NIH/National Cancer Institute. 25 August 2004.
  10. PMID 9776239
    .
  11. PMID 11720463
    .
  12. PMID 19890354
    .
  13. PMID 28791314
    .
  14. PMID 15169607
    .
  15. PMID 19101707
    .
  16. PMID 23144614
    .
  17. PMID 21738474
    .
  18. PMID 23474680
    .
  19. PMID 32188744
    .
  20. PMID 32188752
    .
  21. ^
    PMID 4328814
    .
  22. ^
    S2CID 5843939
    .
  23. PMID 18295550
    .
  24. PMID 8129041
    .
  25. S2CID 38744505
    .
  26. PMID 13889129
    .
  27. PMID 205947
    .
  28. S2CID 1634424
    .

External links

Wikimedia Commons has media related to Simian virus 40.

CDC FAQ

Other

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