17 July 2003 8:00 GMT

by Tabitha M. Powledge

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Washington DC - Evidence mounts that the monkey virus that contaminated early polio vaccines causes human cancer - sometimes in people who never got the vaccine.

Janet Butel has worked on SV40 for much of her long career, but to her the monkey virus is an emerging pathogen. She argues that researchers are in the midst of a changing paradigm for SV40, which contaminated certain polio vaccines nearly half a century ago and is suspected of leaving behind a legacy of cancer.

The idea that the virus is present in some characteristic tumors is no longer controversial, says Butel, who chairs the department of molecular virology and microbiology at Baylor College of Medicine in Houston. The next step is to demonstrate unequivocally that the virus causes those tumors.

Butel, who was speaking at the annual meeting of the American Association for Cancer Research (AACR) here in Washington, wants to understand the interaction of SV40 with its human host.

"Specifically we need to know the details of the immune response to an SV40 infection, both humoral immunity and cellular immunity," she said. She also wants to know which tissues get infected, how the virus is distributed in different cells around the body, and whether it is produced or just goes into a latent phase. "I hope that funding agencies will support these types of studies because it's important for scientists and public health officials to know what risk is posed by SV40 infections," she told BioMedNet News.

SV40 is, no question, a powerful cancer virus. In the hamster, the model animal for SV40 infection, the virus causes tumors of brain and bone as well as lymphomas and mesotheoliomas - exactly the same as cancers seen in people with SV40-positive tumors.

In a metaanalysis published just last month in the American Journals of Medicine, Butel and her colleagues report that in 13 studies, specimens from patients with brain tumors were almost four times more likely to have evidence of SV40 infection than were those from controls. The association was even stronger for 15 mesothelioma papers and four studies on bone cancer. SV40 DNA was also more frequent in three studies of samples from patients with non-Hodgkin's lymphoma.

The strong association with mesotheliomas turns up despite some negative studies. SV40 has important effects on mesosthelial cells in vitro, Butel says; transformation frequency is a thousand times higher than the rate reported for other cells. "It's very important that we study the correct target cells," she urged.

Butel's lab has also described several different SV40 strains, which she says is a relatively new concept. The researchers have sequenced about a dozen genomes so far. "We can tell each lab strain apart," she notes - crucial for establishing that the sequences found in human tumors are not lab strains. A key finding is that some human tumor-associated strains are the same as SV40 from early polio vaccines. The vaccine strains are found in brain tumors and non-Hodgkins lymphoma.

Alarmingly, some patients whose tumors contain the polio vaccine strains are too young to have received the contaminated vaccine. How the patients got exposed to these viruses is a mystery. One possibility, Butel suggests, is that the virus may be transmitted in urine. Studies on immunocompromised patients suggest that route of transmission, and one old study has reported that infected infants shed SV40 in their stools. "A student in my lab has shown that it can be transmitted in utero in hamsters," she added. That's a theoretical possibility in people, although there is no evidence for it. "We don't know; there are several possibilities," she said.

What are the biological differences among these strains, and do they differ in oncogenic potential? Unpublished work from her lab suggests the answer is yes, at least in syrian hamsters.

Butel notes that there are some negative reports arguing no association between SV40 and particular tumors. She speculates that the explanation is geography. SV40 tends to be found in particular US tumors, but not detected in those same tumors in Finland, Turkey, and Austria. "We need to sort this out to see what it's telling us," she said. One explanation may be that contaminated polio vaccine was never used in these countries, Butel speculates.