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, 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. In rats, the oncogenic SV40 Large T-antigen was used to establish a brain tumor model for PNETs and medulloblastomas. ^[2]

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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p53 Damage

SV40 is believed to suppress the transcriptional properties of the tumor-suppressing p53 in humans through the SV40 Large T-antigen and SV40 Small T-antigen. p53 is responsible for initiating 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.

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^[3] 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 knowingly.

Polio has cure.

Treatment in the popular press

Claims have been made detailing the controversy surrounding SV40 research.^[4][5] 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.^[6] The book further alleges falsification of research due to financial conflicts of interest.^[7][8] An additional book written by convicted felon Kevin Trudeau, the creator of the "Natural Cures" infomercial alleges that harm caused to the public by the SV40 virus in polio vaccines has been covered up.

Many of the claims made in the popular press or by lobbying organizations^[9] have minimal support in the scientific literature.

Latest research references

• Kroczynska B, Cutrone R, Bocchetta M, Yang H, Elmishad A, Vacek P, Ramos-Nino M, Mossman B, Pass H, Carbone M (2006). "Crocidolite asbestos and SV40 are cocarcinogens in human mesothelial cells and in causing mesothelioma in hamsters". Proc Natl Acad Sci U S A 103 (38): 14128-33. PMID 16966607.

• Pershouse M, Heivly S, Girtsman T (2006). "The role of SV40 in malignant mesothelioma and other human malignancies". Inhal Toxicol 18 (12): 995-1000. PMID 16920674.

References

1. ^ Fiers W et al., Complete nucleotide-sequence of SV40 DNA, Nature, 273, 113-120, 1978
2. ^ Eibl RH, Kleihues P, Jat PS, Wiestler OD (1994) A model for primitive neuroectodermal tumors in transgenic neural transplants harboring the SV40 large T antigen. Am J Pathol. 1994 Mar;144(3):556-64
3. ^ Vaccine scandal revives cancer fear, Debbie Bookchin, New Scientist, 07 July 2004
4. ^ Rogue virus in the vaccine: Early polio vaccine harbored virus now feared to cause cancer in humans, William Carlsen, San Francisco Chronicle, Sunday, July 15, 2001
5. ^ The Virus and the Vaccine, The Reading Room, WNYC website.
6. ^ The Virus and the Vaccine, Debbie Bookchin and Jim Schumacher, St. Martin's Press, 2004, ISBN: 0-3122-7872-1
7. ^ The Virus and the Vaccine official website
8. ^ The Virus and the Vaccine, Debbie Bookchin and Jim Schumacher, Atlantic Monthly, February 2000.
9. ^ SV40 Cancer Foundation 'SV40 stands for Simian Virus 40', SV40 Cancer Foundation official website