The relationship between simian virus 40 and mesothelioma

Our plain-English summary of The relationship between simian virus 40 and mesothelioma, by Z. Rivera, O. Strianese, P. Bertino, et al (Current Opinion in Pulmonary Medicine, 2008).

The study

• Authors: Z. Rivera, O. Strianese, P. Bertino, H. Yang, H. Pass, M. Carbone
• Journal: Current Opinion in Pulmonary Medicine
• Published: 2008;14(4):316-21
• Type of article: Review
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose Of Review: Simian virus 40 is present in some human malignant mesotheliomas. The evidence in favor and against a pathogenic role of simian virus 40 in malignant mesothelioma is discussed in this review.

Recent Findings: When simian virus 40 is injected intracardially into hamsters, 60% develop and die of malignant mesothelioma. Moreover, some human malignant mesotheliomas contain and express simian virus 40 DNA and proteins. To date, over 50 laboratories have detected simian virus 40 in malignant mesotheliomas and in other tumors; however, the variability of the percentage of positivity led to a controversy about the role and significance of simian virus 40 in malignant mesotheliomas. Compared with other cell types, human mesothelial cells are unusually susceptible to simian virus 40-induced malignant transformation. The presence of simian virus 40 in malignant mesothelioma has been associated with the activation of specific oncogene pathways. Cocarcinogenesis between simian virus 40 and asbestos in causing malignant mesotheliomas has been demonstrated in three separate research laboratories using different experimental approaches. Epidemiological data possibly linking simian virus 40 and malignant mesothelioma is lacking owing to unattainable identification of infected from noninfected cohorts.

Summary: Available evidence appears sufficient to link simian virus 40 either alone or in conjunction with asbestos in causing malignant mesotheliomas; however, it is still insufficient to speculate about the contribution of simian virus 40 to the overall incidence of malignant mesotheliomas.

In plain English

This article was a review, not a new study. The authors summarized published laboratory, animal and human-tumor research on whether simian virus 40 (SV40) plays a role in malignant mesothelioma, alone or with asbestos. SV40 is a monkey virus that contaminated polio vaccines distributed between 1954 and 1978. The review reported that 60% of hamsters injected with SV40 into the heart developed and died of malignant mesothelioma. Over 50 laboratories had detected SV40 in malignant mesotheliomas and other tumors, though at varying rates. One cited group first found SV40 in 67% of biopsies, then judged only 6% truly positive because of laboratory contamination. In cited cell studies, about 80% of human mesothelial cells survived SV40 infection. In a cited hamster study, mutant SV40 alone caused no mesothelioma, but with asbestos it caused mesothelioma in 90% of animals. The authors concluded that the evidence appeared sufficient to link SV40, alone or with asbestos, to causing malignant mesothelioma. They also concluded it was insufficient to judge SV40's contribution to overall mesothelioma rates, because epidemiological studies could not reliably separate infected from uninfected groups.

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: Narrative review of published research
• Who was studied: No study population of its own. The review discussed published cell-culture studies, animal studies (hamsters, mice) and studies testing human mesotheliomas and other tumors for SV40.
• Exposure: Simian virus 40 infection, alone or combined with asbestos. The authors linked SV40 to contaminated polio vaccines distributed between 1954 and 1978, and possibly to other sources. The review text does not name the asbestos fiber type in the studies it describes.
• Main results:
  • Hamsters injected with SV40 into the heart: 60% developed and died of malignant mesothelioma (as summarized by the review)
  • Over 50 laboratories had detected SV40 in malignant mesotheliomas and in other tumors (counted together), though the percentage of positive samples varied
  • Lopez-Rios et al. (a cited study) initially detected SV40 in 67% of their malignant mesothelioma biopsies
  • Lopez-Rios et al. later found only 6% of those biopsies were truly positive; the rest were false positives from laboratory plasmid contamination
  • In cited cell-culture work, about 80% of human mesothelial cells infected with SV40 survived the infection, whereas fibroblasts are usually lysed
  • Bocchetta et al. (cited): human mesothelial cells exposed in culture to both asbestos and a mutant SV40 were transformed; neither agent alone transformed them
  • Kroczynska et al. (cited), in hamsters: mutant SV40 dl883 alone caused no malignant mesothelioma, while asbestos plus dl883 together caused it in 90% of animals. The asbestos-alone figure is printed as '20 of exposed hamsters'.
  • In SV40-infected hamsters, significantly lower amounts of asbestos were sufficient to induce malignant mesothelioma (cited study)
  • Robinson et al. (cited): transgenic mice expressing SV40 Tag were more susceptible to asbestos carcinogenesis than wild-type mice
  • A cited WHO-promoted multi-laboratory study found that polio vaccines produced in the former USSR contained infectious SV40 until 1978. The authors offered this as a possible explanation for geographical differences.
• The authors' conclusion: The authors concluded that available evidence appeared sufficient to link SV40, alone or with asbestos, to causing malignant mesothelioma. They also concluded the evidence was still insufficient to speculate about SV40's contribution to the overall incidence of mesothelioma.
• Limitations the authors state:
  • Epidemiological data linking SV40 and mesothelioma are lacking because infected and uninfected groups cannot be identified
  • Because studies reported different percentages of positivity, the exact percentage of mesotheliomas containing SV40 cannot be established
  • Some studies lacked proper controls and may have reported false-positive results from PCR contamination

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Malignant Mesothelioma, Mesothelial Cells, Malignant Transformation.

Related studies

• Molecular pathogenesis of malignant mesothelioma and its relationship to simian virus 40 — A.F. Gazdar, M. Carbone (2003)
• Progressive aberrant methylation of the RASSF1A gene in simian virus 40 infected human mesothelial cells — S. Toyooka, M. Carbone, et al. (2002)
• Simian virus 40 transformation, malignant mesothelioma and brain tumors — F. Qi, M. Carbone, et al. (2011)
• Asbestos, Simian virus 40 and malignant mesothelioma — S.C. Stenton (1997)
• Simian virus-40 large-T antigen binds p53 in human mesotheliomas — M. Carbone, P. Rizzo, et al. (1997)
• Human mesothelial cells are unusually susceptible to simian virus 40-mediated transformation and asbestos cocarcinogenicity — M. Bocchetta, I. Di Resta, et al. (2000)

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