SV40: A human pathogen?

Our plain-English summary of SV40: A human pathogen?, by R.L. Garcea (Disease Markers, 2001).

The study

• Author: R.L. Garcea
• Journal: Disease Markers
• Published: 2001;17(3):149-51
• Type of article: Review
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Over the past eight years an increasing number of investigators have found SV40 genomic sequences in a variety of human samples, both malignant and normal. Tumor types recurrently reported as SV40-positive include choroid plexus neoplasms, ependymomas, osteosarcomas, and mesotheliomas. Nonetheless, considerable skepticism that SV40 is a human pathogen still prevails. More constructively, the study of SV40 in humans has renewed interest in the related BK and JC viruses and their role in human disease. New questions now must be addressed. In particular, seroepidemiologic studies utilizing reagents that distinguish SV40, BKV, and JCV immune responses would be a logical next step for independently assessing viral prevalence. Also, prospective studies of select patient groups using optimized detection methods might determine whether SV40 is associated with human oncogenesis in particular circumstances. The importance of such research is underscored by the potential to prevent human polyomavirus infections, and possible associated malignancy, through immunization of high risk populations.

In plain English

This short article was a commentary and review that reported no new patient data. The author looked back on published reports, mostly since 1992, that used a laboratory method called PCR to find genetic material from simian virus 40 (SV40) in human tumors, including mesotheliomas, childhood brain tumors and bone tumors. SV40 is a monkey virus that contaminated the Salk polio vaccine. Asbestos was not discussed. The author wrote that SV40-like sequences reported in mesotheliomas had been verified in many laboratories, and listed evidence the author saw as supporting the findings. The author also described problems. Detection often needed 40 to 60 PCR cycles, and results were not consistently reproducible between laboratories. Estimates suggested about 1 viral genome per 10 tumor cells. Epidemiologic studies had failed to confirm more tumors in people who received contaminated vaccine, though the author considered those studies based on narrow assumptions. The author concluded that blood (serologic) tests able to tell SV40 apart from the related BK and JC viruses, together with prospective studies of selected patient groups, were the next step.

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: Commentary and narrative review of published research on SV40 in human tissues; no new data reported
• Who was studied: No study population of its own; the article discusses earlier published reports on SV40 in human tumors (choroid plexus neoplasms, ependymomas, bone tumors, mesotheliomas) and other tissues
• Exposure: Simian virus 40 (SV40), described as a contaminant of the Salk polio vaccine, and the related human BK and JC viruses; asbestos is not discussed
• Main results:
  • The author reported that SV40-like sequences found in mesotheliomas by another research group (Carbone et al.) had since been verified in many laboratories
  • The author described PCR detection of SV40 in tumor tissue as difficult, commonly requiring 40 to 60 PCR cycles
  • The author wrote that difficulty in amplifying SV40 sequences had raised skepticism about the findings, and that technical difficulties may have led to a lack of reproducibility between laboratories
  • The author listed several independent observations that, in the author's view, suggest SV40 identification is valid, including DNA sequencing, a single 72 base pair repeat element, Southern blot detection in osteosarcomas, and recovery of SV40 virus from a human choroid plexus tumor
  • Viral copy number calculations cited by the author estimated 1 viral genome per 10 tumor cells, which the author said confounds cause-effect explanations and raises questions about PCR contamination
  • The author noted that epidemiologic studies had failed to confirm increased tumor incidence in recipients of SV40-contaminated polio vaccines, but considered those studies to rest on narrow assumptions
• The authors' conclusion: The author concluded that serologic assays able to distinguish BKV, JCV and SV40 immune responses, combined with improved PCR methods applied prospectively to defined patient groups, were the next step in resolving whether these viruses, including SV40, are relevant to human tumor development. The author also wrote that if their T-antigens act as co-carcinogens, preventing infection could become an avenue for cancer prevention.
• Limitations the authors state:
  • The author noted that limited space prevented complete citation of all related work

Topics

Medical terms in this study, explained in our Lexicon: SV40, Neoplasm, Mesothelioma, Carcinogenesis.

Related studies

• Increasing evidence for involvement of SV40 in human cancer — J.S. Butel (2001)
• Evidence against a role for SV40 infection in human mesotheliomas and high risk of false-positive PCR results owing to presence of SV40 sequences in common laboratory plasmids — F. López-Ríos, P.B. Illei, et al. (2004)
• Aberrant methylation profile of human malignant mesotheliomas and its relationship to SV40 infection — M. Suzuki, S. Toyooka, et al. (2005)
• The role of SV40 in malignant mesothelioma and other human malignancies — M.A. Pershouse, S. Heivly, et al. (2006)
• SV40 enhances the risk of malignant mesothelioma among people exposed to asbestos: a molecular epidemiologic case-control study — A. Cristaudo, R. Foddis, et al. (2005)
• Cellular and molecular parameters of mesothelioma — M.E. Ramos-Nino, J.R. Testa, et al. (2006)

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