Progressive multifocal leukoencephalopathy: molecular biology, pathogenesis and clinical impact

Our plain-English summary of Progressive multifocal leukoencephalopathy: molecular biology, pathogenesis and clinical impact, by T. Weber, E.O. Major (Intervirology, 1997).

The study

• Authors: T. Weber, E.O. Major
• Journal: Intervirology
• Published: 1997;40(2-3):98-111
• Type of article: Review
• Cited by: 85 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The human polyomaviruses JC virus (JCV) and BK virus (BKV) have long been known as onco- and neurooncogenic. Interest in their oncogenic potential has reemerged with the discovery of simian virus 40 DNA in human brain tumors including the pituitary as well as in bone tumors and mesotheliomas. The only human disease caused by an infection with the human polyomavirus JCV is progressive multifocal leukoencephalopathy (PML) characterized by a lytic infection of oligodendrocytes with consecutive demyelination. Malignant transformation of cell lines appears to be caused by a complex interaction of the viral large T (tumor) antigen with several transcription factors and tumor suppressor proteins such as p53 and the retinoblastoma protein. PML, once an extremely rare disease, has become much more frequent in the western world owing to the AIDS pandemic. An exceedingly complicated, cell-, tissue- and species-specific pattern of protein-DNA interaction and negative as well as positive feedback regulation by at least a dozen proteins and possibly mutations in the JC viral promoter-enhancer region govern host range and development of PML. The intricate molecular and immunological prerequisites ultimately leading to PML in humans have not yet been completely elucidated.

In plain English

This article was a review, not a new study. The authors summarized published research on the human polyomavirus JC virus (JCV) and the brain disease it causes, progressive multifocal leukoencephalopathy (PML). The article did not study asbestos. Mesotheliomas came up only in passing, in the article's opening summary and introduction, where the authors noted that other researchers had reported simian virus 40 (SV40) DNA in human brain tumors, bone tumors and mesotheliomas. The authors described the association of SV40 with human diseases such as brain and bone tumors as still not proven. Citing other studies, the review reported that up to 85% of PML cases occurred in HIV-infected individuals, that average survival was 4 to 6 months, and that PCR testing of spinal fluid had an overall sensitivity of 75% and an overall specificity of 98.5%. The authors noted that only one report had suggested a link between JCV and a human brain tumor. The authors concluded that, on balanced evidence, no PML treatment reported so far had definite efficacy. They also concluded that the conditions leading to PML had not been completely elucidated.

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 on JC virus and progressive multifocal leukoencephalopathy
• Who was studied: No new patients or subjects were studied. The review drew on published literature about JC virus (JCV) and progressive multifocal leukoencephalopathy (PML), including patients with AIDS and other immunosuppressed patients, animal experiments and laboratory studies.
• Exposure: Infection with the human polyomavirus JC virus. Simian virus 40 (SV40) and BK virus were discussed more briefly. No asbestos or fiber exposure was studied or discussed.
• Main results:
  • In the opening summary and the introduction, the authors noted that SV40 DNA had been reported in human brain tumors, bone tumors and mesotheliomas, citing other studies. They stated that the association of SV40 with human diseases such as brain and bone tumors was still not proven.
  • Citing other studies, the review reported that up to 85% of all PML cases occurred in HIV-infected individuals.
  • Citing other studies, the review reported that average survival with PML was 4 to 6 months, although rare survival of up to 10 years had been reported.
  • From published studies, the review reported that PCR of cerebrospinal fluid for PML had an overall sensitivity of 75%. Specificity ranged from 92 to 100%, with an overall specificity of 98.5%.
  • In earlier animal experiments reviewed here, JCV (Mad-1 strain) injected into the brains of hamsters produced brain tumors in over 80% of animals.
  • The authors reported that only one report suggested an association of JCV with human brain tumors (an oligoastrocytoma). Previous studies had failed to detect JCV or JCV DNA in over 100 human brain tumors.
• The authors' conclusion: The authors concluded that the molecular and immunological prerequisites leading to PML in humans had not yet been completely elucidated. They also concluded that, on balanced evidence, no definite efficacy of any treatment reported so far could be ascertained.

Topics

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

Related studies

• New molecular and epidemiological issues in mesothelioma: role of SV40 — M. Carbone, S. Fisher, et al. (1999)
• SV40 and the pathogenesis of mesothelioma — P. Rizzo, M. Bocchetta, et al. (2001)
• Malignant mesothelioma tumours: molecular pathogenesis, diagnosis, and therapies accompanying clinical studies — R.K. Sahu, S. Ruhi, et al. (2023)
• Mesothelioma mortality in Europe: impact of asbestos consumption and simian virus 40 — K. Leithner, A. Leithner, 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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