Simian virus 40 transformation, malignant mesothelioma and brain tumors

Our plain-English summary of Simian virus 40 transformation, malignant mesothelioma and brain tumors, by F. Qi, M. Carbone, H. Yang, et al (Expert Review of Respiratory Medicine, 2011).

The study

• Authors: F. Qi, M. Carbone, H. Yang, G. Gaudino
• Journal: Expert Review of Respiratory Medicine
• Published: 2011;5(5):683-97
• Type of article: Review
• Cited by: 33 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Simian virus 40 (SV40) is a DNA virus isolated in 1960 from contaminated polio vaccines, that induces mesotheliomas, lymphomas, brain and bone tumors, and sarcomas, including osteosarcomas, in hamsters. These same tumor types have been found to contain SV40 DNA and proteins in humans. Mesotheliomas and brain tumors are the two tumor types that have been most consistently associated with SV40, and the range of positivity has varied about from 6 to 60%, although a few reported 100% of positivity and a few reported 0%. It appears unlikely that SV40 infection alone is sufficient to cause human malignancy, as we did not observe an epidemic of cancers following the administration of SV40-contaminated vaccines. However, it seems possible that SV40 may act as a cofactor in the pathogenesis of some tumors. In vitro and animal experiments showing cocarcinogenicity between SV40 and asbestos support this hypothesis.

In plain English

This article was a review, not a new study. The authors summarized laboratory, animal and human research on simian virus 40 (SV40), a monkey virus that contaminated some polio vaccines, and its possible role in malignant mesothelioma and brain tumors. They reported that published studies found SV40 in roughly 6 to 60% of these tumors, with a few reporting 100% and a few 0%. They also reported that 13 brain tumor studies from 1975 to 2002 found about 18% positive overall. They described earlier experiments, including some from their own group. In these, asbestos alone did not transform human mesothelial cells in culture, but SV40 plus asbestos raised the transformation rate. Hamsters given crocidolite asbestos plus an SV40 strain (dl883) that does not cause mesothelioma on its own developed mesothelioma at about 90%, compared with 20% for asbestos alone. The authors noted that some positive human studies may have been flawed, for example by contamination from laboratory plasmids. They concluded that SV40 alone appears unlikely to cause human cancer but may act as a cofactor, and that its possible role needs further study.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review of published research on SV40 biology, SV40 cancer-causing effects in cells and animals, SV40 and asbestos acting together, and reports of SV40 in human mesotheliomas and brain tumors
• Who was studied: Published studies, not new patients: laboratory studies of human mesothelial cells and astrocytes, hamster and transgenic mouse experiments, and studies testing human mesothelioma and brain tumor specimens from many countries for SV40
• Exposure: SV40 (a virus that contaminated some polio vaccines) alone and combined with asbestos. In the animal experiments described, this was crocidolite asbestos injected into the pleura and peritoneum of hamsters, together with the dl883 SV40 strain
• Main results:
  • Across published studies of human mesotheliomas and brain tumors, the share of specimens found positive for SV40 ranged from about 6 to 60%; a few studies reported 100% and a few reported 0%
  • In an earlier hamster experiment by the authors' group (reference 73), crocidolite asbestos combined with dl883 SV40 produced mesothelioma in about 90% of hamsters, with a shorter latency. Asbestos alone produced mesothelioma in 20%
  • In cell culture studies cited by the authors, asbestos alone did not transform human mesothelial cells, while combined exposure to SV40 and asbestos increased the transformation rate
  • Thirteen studies published between 1975 and 2002, reviewed elsewhere, reported an overall prevalence of about 18% of brain tumors containing SV40 sequences
  • Some research groups did not detect SV40 in mesothelioma biopsies
  • In one cited study (Lopez-Rios et al.), an initial 52 to 62% SV40 positivity in mesotheliomas was linked to primers matching common laboratory plasmids. With different primers, only 6% of the mesothelioma biopsies were confirmed positive
  • Studies using blood tests (ELISA) that distinguish SV40 from the human polyomaviruses JC and BK found anti-SV40 antibodies in 1% of those tested
• The authors' conclusion: The authors concluded that SV40 infection alone appears unlikely to be enough to cause human cancer, but that SV40 may act as a cofactor. They wrote that at least 5% of human mesotheliomas and brain tumors appear to contain SV40 DNA, and that its possible role in causing these tumors should be investigated further.
• Limitations the authors state:
  • Some studies reporting SV40 in human tumors may have been flawed and may have overestimated how often SV40 is present
  • Some studies found SV40 DNA but no SV40 proteins, which leaves open whether the DNA alone has any role in causing disease
  • The exact mechanisms by which SV40 and asbestos act together are unknown
  • The authors stated they do not know how to study 'hit and run' cancer causation by SV40 in humans

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, SV40, Mesothelioma, Sarcoma.

Related studies

• Simian virus 40 sequences in blood specimens from healthy individuals of Casale Monferrato, an industrial town with a history of asbestos pollution — C. Pancaldi, V. Balatti, et al. (2009)
• Evaluation of simian virus-40 as a biological prognostic factor in Egyptian patients with malignant pleural mesothelioma — A.R. Zekri, A.A. Bahnassy, et al. (2007)
• Cellular and molecular parameters of mesothelioma — M.E. Ramos-Nino, J.R. Testa, et al. (2006)
• Mesothelioma mortality in Europe: impact of asbestos consumption and simian virus 40 — K. Leithner, A. Leithner, et al. (2006)
• Human mesotheliomas contain the simian virus-40 regulatory region and large tumor antigen DNA sequences — H.I. Pass, J.S. Donington, et al. (1998)
• No association between simian virus 40 and diffuse malignant mesothelioma of the pleura in Iranian patients: a molecular and epidemiologic case-control study of 60 patients — Z. Mohammad-Taheri, S.A. Nadji, et al. (2013)

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