Simian virus 40 in humans

Our plain-English summary of Simian virus 40 in humans, by F. Martini, A. Corallini, V. Balatti, et al (Infectious Agents and Cancer, 2007).

The study

• Authors: F. Martini, A. Corallini, V. Balatti, S. Sabbioni, C. Pancaldi, M. Tognon
• Journal: Infectious Agents and Cancer
• Published: 2007;2:13
• Cited by: 54 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Simian virus 40 (SV40) is a monkey virus that was administered to human populations by contaminated vaccines which were produced in SV40 naturally infected monkey cells. Recent molecular biology and epidemiological studies suggest that SV40 may be contagiously transmitted in humans by horizontal infection, independently from the earlier administration of SV40-contaminated vaccines.SV40 footprints in humans have been found associated at high prevalence with specific tumor types such as brain and bone tumors, mesotheliomas and lymphomas and with kidney diseases, and at lower prevalence in blood samples from healthy donors. Contrasting reports appeared in the literature on the circulation of SV40 in humans by contagious transmission and its association, as a possible etiologic cofactor, with specific human tumors. As a consequence of the conflicting results, a considerable debate has developed in the scientific community. In the present review we consider the main results obtained by different groups investigating SV40 sequences in human tumors and in blood specimens, the putative role of SV40 in the onset/progression of specific human tumors, and comment on the hypotheses arising from these data.

In plain English

This was a narrative review by authors at the University of Ferrara of published work on simian virus 40 (SV40), a monkey virus given to people in 1955-'63 through poliovirus vaccines prepared in naturally SV40-infected monkey cell cultures. The authors summarised the virus's structure and life cycle, its transformation of cells and tumour induction in rodents, serological and PCR surveys in human populations, and its reported association with human tumours. They noted the DNA sequence homology of SV40 with the human polyomaviruses BKV (70%) and JCV (69%) and the resulting antibody cross-reactivity, reported serosurveys ranging from 0.4 to 5.3 per cent and 1.3 to 15.6 per cent positive, and a study finding SV40 seroprevalence similar in cancer patients and controls (5% to 10%). They cited work in which direct inoculation of SV40 into the pleural space induced malignant mesothelioma in 100% of injected hamsters, and reported that asbestos, described as the main cause of human mesothelioma, cooperates with SV40 in transforming murine cells and human fibroblasts and mesothelial cells, suggesting the two may be co-carcinogens.

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 molecular, serological, epidemiological and experimental studies on SV40
• Who was studied: No new participants; the review covered published studies of SV40 in human tumours, blood and other specimens, plus experimental animal and cell studies
• Exposure: SV40 infection, from SV40-contaminated poliovirus and other vaccines (1955-1963) and from possible horizontal transmission; asbestos considered as a co-factor for mesothelioma
• Main results:
  • The review reported that SV40 DNA sequences share 70% homology with BKV and 69% with JCV, the basis for serological cross-reactivity
  • Reviewed serological studies: 100% of a Moroccan collection of 29 sera had SV40 antibodies, while sera from Morocco, Zaire, Sierra Leone and Poland contained SV40 antibodies in 0.4 to 5.3% of samples
  • Other reviewed studies using neutralisation and ELISA found SV40 antibodies in 1.3 to 15.6% of normal human sera, and VLP-based studies found similar seroprevalence in cancer patients and controls (5% to 10%)
  • A reviewed ELISA study using SV40 VP1 virus-like particles detected antibodies in 6,6% of human sera, which disappeared after pre-adsorption with BKV and JCV VLPs; the authors of the review questioned the validity of VLP assays
  • Reviewed animal experiments: inoculation of SV40 into the pleural space induced malignant mesothelioma in 100% of injected hamsters
  • Reviewed cell work: human mesothelial cells were transformed at a rate 1,000 times higher than human fibroblasts, and asbestos cooperated with SV40 in transformation
  • The review reported asbestos and SV40 as possible co-carcinogens in mesothelioma onset
  • Two multi-institutional studies of SV40 in human malignant mesothelioma reached opposite conclusions, according to the review
• The authors' conclusion: The authors summarised the Immunization Safety Review Committee's evaluation that evidence is inadequate to accept or reject a causal relationship between SV40-containing polio vaccines and cancer, while the biological evidence that SV40 is a transforming virus is strong, and noted that the conviction that SV40 acts as a cofactor in some human tumours has prompted vaccine development against SV40 Tag
• Limitations the authors state:
  • The authors stated that the prevalence of SV40 infection in humans is not known and that no comparative data exist on SV40 DNA in PBMC and SV40 antibodies in sera from the same patients
  • The authors stated that antigenic cross-reaction with BKV and JCV has been the most difficult problem in studying SV40 diffusion, and that the validity of VLP-based assays is problematic
  • The authors noted discrepancies in PCR detection, questions about sensitivity, specificity and possible false positives from laboratory plasmid contamination
  • The authors stated that past epidemiological studies were flawed by difficulty identifying who received contaminated vaccines, the dosage of infectious SV40, and the need for decades of follow-up

Topics

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

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)
• Association Between Simian Virus 40 and Human Tumors — J.C. Rotondo, E. Mazzoni, et al. (2019)
• 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)
• The retinoblastoma gene family pRb/p105, p107, pRb2/p130 and simian virus-40 large T-antigen in human mesotheliomas — A. De Luca, A. Baldi, et al. (1997)
• Simian virus 40, poliovaccines and human tumors: a review of recent developments — M. Carbone, P. Rizzo, et al. (1997)

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