Simian Virus 40 and Mesothelioma

Friday, September 30, 2005

Because of the fact that a small percentage, maybe 5%, of people exposed to asbestos develop Mesothelioma, some researchers have wondered if there could be an environmental trigger like a viral infection in addition to genetic factors and asbestos. According to this theory, a viral infection would trigger a cascade of events that led to cancer developing.

A virus called Simian Virus 40 (SV40) has been suggested as a candidate for such a trigger.

SV40 has a rather unusual history. How did a monkey virus come to infect so many people?

In the 1950's and 60's two types of vaccines with widespread use, polio and adenovirus became infected with SV40 through the tissue cultures the vaccines were made with. As a result large numbers of people throughout the world were infected. Some estimates run as high as 96 million adults and children getting the vaccine in the US alone. Now that the virus is present in humans it is transmitted person to person from mother to fetus and by contamination via the fecal-oral pathway. The prevalence of antibodies to SV40 can run as high as 20% in some populations.

SV40 is a known oncogenic virus in laboratory animals. Among the cancers it is known to cause in animals is mesothelioma. A particular protein produced by the virus turns off tumor-suppressor genes. Without the normal brakes on cell division, the cells start to divide out of control.
In the lab cell cultures of normal human mesothelial cells can be transformed to cancerous cells by infecting the culture with SV40.

In animals SV40 requires asbestos exposure for mesothelioma to develop. SV40 alone does not produce mesothelioma in animals. Mesothelioma also develops with asbestos exposure alone, however SV40 speeds up the disease process.

When large samples of mesothelioma tumors were examined, approximately 50% had SV40 proteins or gene sequences.

Clearly SV40 is not necessary for mesothelioma to develop, however it may play a role in accelerating the disease in those who are susceptible. It may be that some of those people infected would never have developed malignant mesothelioma without the infection.

A recent study conducted at Mount Sinai School of Medicine casts doubt on the SV40 hypothesis. In the study they used extremely sensitive diagnostic techniques and carefully controlled for contamination, which they argued was a flaw in earlier studies. They found no evidence of SV40 DNA sequences in any of 69 mesothelioma tumors. If the true rate was 50% then that many specimens should yield some positives.

A previous study showed that the SV40 fragments being detected were actually contaminants from molecular probes used by researchers, not from intact SV40 virus. The study also showed that the assay used to detect SV40 had a high false-positive rate.

The jury is still out on SV40, though both camps pro and con would disagree. Whatever the eventual outcome, it illustrates that science rarely takes a straight path.
SV40