Association Between Simian Virus 40 and Human Tumors

Our plain-English summary of Association Between Simian Virus 40 and Human Tumors, by J.C. Rotondo, E. Mazzoni, I. Bononi, et al (Frontiers in Oncology, 2019).

The study

• Authors: J.C. Rotondo, E. Mazzoni, I. Bononi, M. Tognon, F. Martini
• Journal: Frontiers in Oncology
• Published: 2019;9:670
• Type of article: Review
• Cited by: 67 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Simian virus 40 (SV40) is a small DNA tumor virus of monkey origin. This polyomavirus was administered to human populations mainly through contaminated polio vaccines, which were produced in naturally infected SV40 monkey cells. Previous molecular biology and recent immunological assays have indicated that SV40 is spreading in human populations, independently from earlier SV40-contaminated vaccines. SV40 DNA sequences have been detected at a higher prevalence in specific human cancer specimens, such as the brain and bone tumors, malignant pleural mesotheliomas, and lymphoproliferative disorders, compared to the corresponding normal tissues/specimens. However, other investigations, which reported negative data, did not confirm an association between SV40 and human tumors. To circumvent the controversies, which have arisen because of these molecular biology studies, immunological researches with newly developed indirect ELISA tests were carried out in serum samples from patients affected by the same kind of tumors as mentioned above. These innovative indirect ELISAs employ synthetic peptides as mimotopes/specific SV40 antigens. SV40 mimotopes do not cross-react with the homologous human polyomaviruses, BKPyV, and JCPyV. Immunological data obtained from indirect ELISAs, using SV40 mimotopes, employed to analyze serum samples from oncological patients, have indicated that these sera had a higher prevalence of antibodies against SV40 compared to healthy subjects. The main data on (i) the biology and genetics of SV40; (ii) the epidemiology of SV40 in the general population, (iii) the mechanisms of SV40 transformation; (iv) the putative role of SV40 in the onset/progression of specific human tumors, and (v) its association with other human diseases are reported in this review.

In plain English

This was a narrative review covering the biology and genetics of simian virus 40 (SV40), its epidemiology in human populations, mechanisms of SV40 transformation, and reported associations with human tumours and non-malignant diseases. SV40, a monkey polyomavirus, was described as having been administered to humans mainly through polio vaccines produced in naturally infected monkey cells between 1955 and 1963. The authors tabulated published detections of SV40 DNA, RNA and protein in tumour specimens, and separately anti-SV40 antibodies in serum samples from patients, for tumours including malignant pleural mesothelioma (MPM), brain and bone tumours and lymphoproliferative disorders; reported tissue prevalence varied by region, with 20-83% of MPM SV40-positive in the U.S. and Europe but no detection in MPM from Turkey and Austria. They cited hamster experiments in which SV40 injected into the pleural space induced MPM in 100% of animals, and work in which normal human mesothelial cells exposed to both SV40 and asbestos fibres showed a significantly increased transformation rate. Indirect ELISAs using SV40 mimotopes showed higher antibody prevalence in sera from MPM, glioblastoma multiforme, osteosarcoma and non-Hodgkin's lymphoma patients than in matched healthy subjects, while other investigators reported negative results. The authors concluded that the role of SV40 in human tumours, if any, remains to be proven.

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, immunological, epidemiological and experimental studies
• Who was studied: published studies of SV40 in human tumour and normal specimens, sera from patients and healthy subjects, plus animal and cell-culture experiments; no new patients studied
• Exposure: SV40 infection, mainly introduced through SV40-contaminated polio vaccines (1955-1963); also asbestos fibres as a co-factor in mesothelial cell transformation
• Main results:
  • Reviewed detection rates of SV40 in MPM tissue differed by region: 20-83% positive in the U.S. and Europe, never detected in MPM from Turkey and Austria
  • In hamsters, SV40 injected into the pleural space was reported to induce malignant pleural mesothelioma in 100% of animals
  • Normal human mesothelial cells (HMC) exposed to both SV40 and asbestos fibres were reported to show a significantly increased transformation rate compared with controls
  • In healthy blood donors, IgG antibodies in serum reacting to SV40 VPs and Tag were reported at prevalences of 18% and 20% respectively
  • Indirect ELISAs with SV40 mimotopes gave a significantly higher antibody prevalence in sera of MPM, glioblastoma multiforme, osteosarcoma and non-Hodgkin's lymphoma patients than in matched healthy subjects
  • For malignant pleural mesothelioma, the tabulated serological study reported anti-SV40 antibodies in serum in 25/97 (26%) by ELISA
  • Some reviewed studies found no association, reporting neither viral DNA (or only low-prevalence DNA) nor viral oncoproteins or miRNAs in the same tumour types
• The authors' conclusion: The authors concluded that conflicting results exist, that SV40 or a closely related polyomavirus circulates in humans, and that any role of SV40 in human tumours remains to be proven and needs further investigation
• Limitations the authors state:
  • The authors state the reviewed studies are association studies that cannot prove a causative role for SV40
  • The authors state that these assays did not quantify SV40 DNA copy number or determine whether the viral DNA was integrated or episomal
  • The authors note the risk of false-positive PCR results from laboratory plasmids carrying SV40 sequences
  • The authors state that the serological findings do not exclude that another, still unknown polyomavirus closely related to SV40 circulates in humans

Topics

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

Related studies

• Simian virus 40, poliovaccines and human tumors: a review of recent developments — M. Carbone, P. Rizzo, et al. (1997)
• Human mesotheliomas contain the simian virus-40 regulatory region and large tumor antigen DNA sequences — H.I. Pass, J.S. Donington, et al. (1998)
• Simian virus 40 and human tumors: It is time to study mechanisms — M. Carbone (1999)
• Presence and expression of the simian virus-40 genome in human giant cell tumors of bone — G. Gamberi, M.S. Benassi, et al. (2000)
• Simian virus 40 in humans — F. Martini, A. Corallini, et al. (2007)
• Simian virus-40 large-T antigen binds p53 in human mesotheliomas — M. Carbone, P. Rizzo, et al. (1997)

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