SV40
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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, but most often persists as a latent infection.
The virus was first identified in 1960 in cultures of rhesus monkey kidney cells that were being used to produce polio vaccine. It was named for the effect it produced on infected green monkey cells, which developed an unusual number of vacuoles. The complete DNA sequence of the virus was sequenced by Walter Fiers and his team at the University of Ghent (Belgium) in 1978[1]. The virus is dormant and shows no visible effects in Rhesus monkeys. The virus has been found in many macaque populations in the wild, where it rarely causes disease. However, in monkeys that are immunodeficient—due to, for example, infection with Simian immunodeficiency virus—SV40 acts much like the human JC and BK polyomaviruses, producing kidney disease and sometimes a demyelinating disease similar to PML. In other species, particularly hamsters, SV40 causes a variety of tumors, generally sarcomas.
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.
SV40 has not been proven to cause disease in humans, but several studies have suggested a link to cancer based on the presence of relatively large amounts of what may be SV40 DNA fragments in some tumor tissues, particularly mesotheliomas and non-Hodgkin's lymphoma. There is as yet no consensus on the meaning of these findings.
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[edit] p53 Damage
SV40 is believed to damage the tumor-suppressing p53 gene in humans. The p53 gene is responsible for initiating apoptosis, or "cellular suicide," when a cell is damaged. A damaged p53 gene may contribute to uncontrolled cellular reproduction, leading to a tumor.
[edit] Polio vaccine contamination
Soon after its discovery, SV40 was identified in the injected form of the polio vaccine produced between 1955 and 1961. This is believed to be due to kidney cells from infected monkeys being used to amplify the vaccine virus during production. Both the Sabin vaccine (oral, live virus) and the Salk vaccine (injectable, killed virus) were affected; the technique used to inactivate the polio virus in the Salk vaccine, by means of formaldehyde, did not reliably kill SV40.
It was difficult to detect small quantities of virus until the advent of PCR testing; since then, stored samples of vaccine made after 1962 have tested negative for SV40, but no samples prior to 1962 could be found. Thus, although over 10 million people received the potentially contaminated batches of vaccine, there is no way to know whether they were exposed to the virus, and if so, whether it was in a quantity and by a route that would cause infection. It is also unknown how widespread the virus was among humans before the 1950s, though one study found that 12% of a sample of German medical students in 1952 had SV40 antibodies. It is not known whether the virus can be transmitted between humans.
An analysis presented at the Vaccine Cell Substrate Conference in 2004 [1] suggested that vaccines used in the former Soviet bloc countries, China, Japan, and Africa, could have been contaminated up to 1980, meaning that hundreds of millions more could have been exposed to the virus.
[edit] Treatment in the popular press
Claims have been made detailing the controversy surrounding SV40 research. One book by a pair of investigative journalists contains statements indicating that researchers were penalized for reporting the findings of a potential cause and effect relationship between the early polio vaccine, SV40 and cancer. The book further alleges falsification of research due to financial conflicts of interest. [2]
An additional book written by the creator of the "Natural Cures" infomercial alleges a coverup of harm caused to the public.
[edit] Latest research references
1). Proc Natl Acad Sci U S A. 2006 Sep 11; [Epub ahead of print]
Crocidolite asbestos and SV40 are cocarcinogens in human mesothelial cells and in causing mesothelioma in hamsters.
Kroczynska B, Cutrone R, Bocchetta M, Yang H, Elmishad AG, Vacek P, Ramos-Nino M, Mossman BT, Pass HI, Carbone M.
Thoracic Oncology Program, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL 60153;
Only a fraction of subjects exposed to asbestos develop malignant mesothelioma (MM), suggesting that additional factors may render some individuals more susceptible. We tested the hypothesis that asbestos and Simian virus (SV40) are cocarcinogens. Asbestos and SV40 in combination had a costimulatory effect in inducing ERK1/2 phosphorylation and activator protein-1 (AP-1) activity in both primary Syrian hamster mesothelial cells (SHM) and primary human mesothelial cells (HM). Ap-1 activity caused the expression and activation of matrix metalloprotease (MMP)-1 and MMP-9, which in turn led to cell invasion. Experiments using siRNA and chemical inhibitors confirmed the specificity of these results. The same effects were observed in HM and SHM. Experiments in hamsters showed strong cocarcinogenesis between asbestos and SV40: SV40 did not cause MM, asbestos caused MM in 20% of hamsters, and asbestos and SV40 together caused MM in 90% of hamsters. Significantly lower amounts of asbestos were sufficient to cause MM in animals infected with SV40. Our results indicate that mineral fibers and viruses can be cocarcinogens and suggest that lower amounts of asbestos may be sufficient to cause MM in individuals infected with SV40.
2). Inhal Toxicol. 2006 Nov;18(12):995-1000. The role of SV40 in malignant mesothelioma and other human malignancies.
Pershouse MA, Heivly S, Girtsman T.
Center for Environmental Health Sciences, Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, Montana 59812, USA. mark.pershouse@umontana.edu
SV40 is a DNA tumor virus thrust upon human populations primarily as a contaminant in various vaccine preparations. Some estimates suggest that millions of people are currently infected with the virus. The virus causes primary brain tumors, bone tumors, lymphomas, and mesotheliomas when injected into some rodent models. It has also been detected in a similar spectrum of human tumors. However, epidemiological studies have failed to conclusively demonstrate a higher incidence of disease in affected populations. To date, over 60 reports from 49 different laboratories have shown SV40 sequences in tissues from human cancer patients. Six studies, however, have failed to detect evidence of virus in similar tissues. Some have suggested that SV40 may act as a cocarcinogen with asbestos to cause mesothelioma formation, or that it may be responsible for the 10-20% of mesotheliomas with no reported history of asbestos exposure. This report briefly covers the historical evidence for SV40 carcinogenesis and then covers experiments now underway to better understand the role of SV40 in human mesotheliomas.
[edit] References
- ^ Fiers W et al., Complete nucleotide-sequence of SV40 DNA, Nature, 273, 113-120, 1978
[edit] External links
- CDC.gov - 'Simian Virus 40 (SV40), Polio Vaccine, and Cancer Q&A' (fact sheet), US Center for Disease Control
- FDA.gov - 'Simian Virus 40: A Possible Human Polyomavirus Workshop' (transcript of 1997 NIH conference on SV40 in humans, part 1), National Institutes of Health (NIH)
- SV40Foundation.org - 'SV40 stands for Simian Virus 40', SV40 Foundation
- TheVirusAndTheVaccine.com - ' The Virus and the Vaccine: the true story of a cancer-causing monkey virus, contaminated polio vaccine, and the millions of Americans exposed', Debbie Bookchin, Jim Schumaker (2004), ISBN 0-312-27872-1
