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The meaning of «sv40»

SV40 is an abbreviation for simian vacuolating virus 40 or simian virus 40, a polyomavirus that is found in both monkeys and humans. Like other polyomaviruses, SV40 is a DNA virus that has the potential to cause 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]

The hypothesis that SV40 might cause cancer in humans has been a particularly controversial area of research.[3] It is currently unclear whether SV40 has any role in causing tumors.[4] As a result of these uncertainties, academic opinion remains divided, with some arguing that this hypothesis is not supported by the data[5] and others arguing that some cancers may involve SV40.[6][7] The US National Cancer Institute announced in 2004 that although SV40 does cause cancer in some animal models, "substantial epidemiological evidence has accumulated to indicate that SV40 likely does not cause cancer in humans".[8] This announcement was based on two studies.[9][10] This 2004 announcement is in contrast to a 2002 study performed by The National Academy of Sciences Immunization Safety Review committee that stated, "The committee concludes that the biological evidence is moderate that SV40 exposure could lead to cancer in humans under natural conditions.”[11]

SV40 may act as a co-carcinogen with crocidolite asbestos to cause mesothelioma.[12][13] The mechanism may involve suppression of the transcriptional properties of tumor suppressor p53 in humans by the SV40 large T antigen and SV40 small T-antigen. Tumor suppressor p53 is responsible for initiating regulated cell death ("apoptosis"), or cell cycle arrest when a cell is damaged. A mutated p53 gene may contribute to uncontrolled cellular proliferation, leading to a tumor.

Some vaccines made in the USA 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,[14] though SV40 has been extensively studied.[15] A thirty-five year follow-up did not find excess numbers of cancers associated with SV40.[16]

SV40 consists of an unenveloped icosahedral virion with a closed circular double-stranded DNA genome[17] of 5.2 kb.[18] The virion adheres to cell surface receptors of MHC class I by the virion glycoprotein VP1. Penetration into the cell is through a caveolin vesicle. Inside the cell nucleus, the cellular RNA polymerase II acts to promote early gene expression. This results in an mRNA that is spliced into two segments. The small and large T antigens result from this. The large T antigen has two functions: 5% goes to the plasma cell membrane and 95% returns to the nucleus. Once in the nucleus the large T antigen binds three viral DNA sites, I, II and III. Binding of sites I and II autoregulates early 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 is has been reported to act as a viroporin facilitiating release of viral particles and resulting in cytolysis;[19][20] however the presence and role of VP4 have been disputed.[21][22]

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