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. 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&mdash;due to, for example, infection with Simian immunodeficiency virus&mdash;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.

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.

Some have hypothesized that SV40 can cause cancer in humans. This conjecture was supported by studies indicating that SV40 is present in a significant subset of human tumor tissues, such brain tumors, bone cancers, malignant mesothelioma, and non-Hodgkin's lymphoma. . In addition, SV40 may act as a cocarcinogen with crocidolite to cause mesothelioma (review )

However, the United States National Cancer Institute has announced that there is no evidence that SV40 causes cancer in humans. This announcement is based on two recent studies.

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 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.

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. An additional book written by 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.

CDC FAQ

 * Frequently Asked Questions about Cancer, Simian Virus 40 (SV40), and Polio Vaccine, Science Coordination and Innovation, United States Centers for Disease Control

NIH 1997 Conference on SV40

 * Simian Virus 40 (SV40:) A Possible Human Polyomavirus Workshop Monday January 27, 1997, Morning Session, transcript of 1997 National Institutes of Health conference on SV40 in humans, (part 1 of 3), United States Food and Drug Administration (FDA)
 * Simian Virus 40 (SV40:) A Possible Human Polyomavirus Workshop Monday January 27, 1997 Afternoon Session, transcript of 1997 National Institutes of Health conference on SV40 in humans (part 2 of 3), United States Food and Drug Administration (FDA)
 * Simian Virus 40 (SV40:) A Possible Human Polyomavirus Workshop, Tuesday, January 28, 1997, transcript of 1997 National Institutes of Health conference on SV40 in humans  (part 3 of 3 ), United States Food and Drug Administration (FDA)

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