Simian virus 40 and the human mesothelium

Our plain-English summary of Simian virus 40 and the human mesothelium, by G. Klein (Proceedings of the National Academy of Sciences of the United States of America, 2000).

The study

• Author: G. Klein
• Journal: Proceedings of the National Academy of Sciences of the United States of America
• Published: 2000;97(18):9830-1
• Type of article: Comment
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Summary of the article

This commentary discussed a companion study by Bocchetta et al., published in the same issue of PNAS, on how simian virus 40 (SV40) interacts with human mesothelial cells. The author described how DNA tumor viruses can cause tumors and noted that the SV40 large T protein inactivates both the retinoblastoma and p53 pathways. He summarized the companion findings. SV40 infection of human mesothelial cells was nonlytic, T-antigen was made in 100% of the cells, and transformed foci appeared at more than 1,000-fold higher efficiency than in human fibroblasts infected in parallel. Most mesothelial foci contained immortalized cells. Bocchetta et al. attributed this to the higher p53 level in mesothelial cells, a view supported by antisense p53 experiments. The author noted that SV40 DNA has frequently been reported in about two-thirds of malignant mesotheliomas. In the companion study, crocidolite asbestos caused only a moderate increase in focus formation with one SV40 plasmid. It rescued focus formation with another plasmid that induced no foci on its own. Its high toxicity to mesothelial cells was counteracted by transforming SV40 plasmids. The author judged these asbestos effects too minor to account for mesothelioma in vivo. He discussed possible roles for asbestos through immunosuppression, oxygen radicals from macrophages, or genetic changes. He concluded that the findings were consistent with, but did not prove, a role for SV40 in some human mesotheliomas, and that how SV40 reaches the human mesothelium remained to be clarified.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This was a short commentary by George Klein on a laboratory study by Bocchetta and colleagues in the same journal issue, with no new data of its own. As described, that study infected cultured human mesothelial cells and fibroblasts with simian virus 40 (SV40). The virus did not destroy the mesothelial cells. Transformed growths (foci) appeared in mesothelial cultures at more than 1,000-fold higher efficiency than in fibroblasts, and most contained immortalized cells. The study also added crocidolite asbestos. Asbestos only moderately increased foci in cells given plasmids carrying both the large and small T antigens of SV40. With another plasmid type that produced no foci on its own, asbestos restored focus formation to nearly that level. Asbestos was highly toxic to mesothelial cells; the SV40 plasmids counteracted this. The author concluded the findings were consistent with, but did not prove, a role for SV40 in some human mesotheliomas. The author also wrote that these minor asbestos effects could hardly account for mesothelioma in the body. Whether the mesothelial foci could form tumors was unknown, the author noted.

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 on a companion laboratory (cell culture) study by Bocchetta et al.; no original data
• Who was studied: No study population of its own. It discusses Bocchetta et al.'s experiments on cultured human mesothelial (HM) cells and human fibroblasts (HFs).
• Exposure: In the discussed study: SV40 infection or SV40 plasmids, with and without crocidolite asbestos, in cell cultures
• Main results:
  • As reported from Bocchetta et al.: SV40's interaction with human mesothelial cells was nonlytic, and T-antigen was made in 100% of the cells
  • As reported from Bocchetta et al.: transformed foci appeared in mesothelial cultures at more than 1,000-fold higher efficiency than in fibroblast cultures infected in parallel
  • As reported from Bocchetta et al.: most mesothelial foci grew at low serum and in soft agar and contained immortalized cells, unlike fibroblast foci
  • Bocchetta et al. attributed the mesothelial cells' high transformability to their higher p53 level. Blocking p53 (antisense p53) increased viral DNA replication and caused cell lysis in infected mesothelial cells.
  • As reported from Bocchetta et al.: crocidolite asbestos caused only a moderate increase in foci in mesothelial and fibroblast cells given plasmids carrying both large and small T antigen
  • As reported from Bocchetta et al.: another plasmid type induced no foci in either cell type. Adding asbestos restored focus formation to a level nearly comparable to the plasmids carrying both T antigens.
  • As reported from Bocchetta et al.: asbestos was highly toxic to mesothelial cells (but not fibroblasts), and this was counteracted by the transforming SV40 plasmids
• The authors' conclusion: The author concluded that transformation of SV40-transfected mesothelial cells, but not fibroblasts, is consistent with, but does not prove, a role for SV40 in some human mesotheliomas. The author also concluded that the minor in vitro effects of asbestos can hardly explain mesothelioma induction in the body.
• Limitations the authors state:
  • It was not known whether the SV40-induced mesothelial foci are tumorigenic
  • The asbestos effects seen in vitro were relatively minor and can hardly account for mesothelioma in the body
  • How SV40 reaches the human mesothelium remains unresolved. So does whether the SV40 sequences found in mesotheliomas match the simian virus or come from a distinct variant.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelium, SV40, Mesothelial Cells, Fibroblast, Malignant Mesothelioma, Crocidolite, Mesothelioma, Macrophage.

Related studies

• Human mesothelial cells are unusually susceptible to simian virus 40-mediated transformation and asbestos cocarcinogenicity — M. Bocchetta, I. Di Resta, et al. (2000)
• Simian virus 40 infection down-regulates the expression of nitric oxide synthase in human mesothelial cells — E. Aldieri, S. Orecchia, et al. (2004)
• The presence of simian-virus 40 sequences in mesothelioma and mesothelial cells is associated with high levels of vascular endothelial growth factor — P. Cacciotti, L. Strizzi, et al. (2002)
• Simian virus-40 large-T antigen binds p53 in human mesotheliomas — M. Carbone, P. Rizzo, et al. (1997)
• 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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