Association of human herpesvirus 6 with the demyelinative lesions of progressive multifocal leukoencephalopathy

David J. Mock, James M. Powers, Andrew D. Goodman, Shira R. Blumenthal, Nurcan Ergin, Jeffrey V. Baker, David H. Mattson, Jose G. Assouline, Earl J. Bergey, Bojun Chen, Leon G. Epstein, Benjamin M. Blumberg

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Progressive Multifocal Leukoencephalopathy (PML) is a primary demyelinating disease of the central nervous system occurring almost exclusively in individuals with impaired cell-mediated immunity. The JC polyoma virus has been accepted as the etiologic agent of PML. Using a two-step in-situ polymerase chain reaction procedure to amplify and detect genomic DNA of human herpesvirus-6 (HHV6) in formalin-fixed paraffin-embedded archival brain tissues, a high frequency of infected cells was consistently detected in PML white matter both within and surrounding demyelinative lesions and HHV6 genome was found mainly within oligodendrocytes. Lesser amounts of HHV6 genome were detected in most normal, AIDS, and other neurological disease control tissues. Immunocytochemistry for HHV6 antigens showed actively infected nuclei of swollen oligodendrocytic morphology only within the demyelinative lesions of PML but not in adjacent uninvolved tissue. In addition, no HHV6 antigens were detectable in control tissues including brains of individuals with HIV-1 encephalopathy but without PML. Double immunohistochemical staining for JC virus large T antigen and HHV6 antigens demonstrated co-labeling of many swollen intralesional oligodendrocytes in the PML cases. The evidence suggests that HHV6 activation in conjunction with JC virus infection is associated with the demyelinative lesions of PML.

Original languageEnglish (US)
Pages (from-to)363-373
Number of pages11
JournalJournal of NeuroVirology
Volume5
Issue number4
DOIs
StatePublished - Aug 1999
Externally publishedYes

Keywords

  • Co-infection
  • Demyelination
  • Human Herpesvirus 6
  • JCV
  • Pathogenesis
  • Progressive Multifocal Leukoencephalopathy

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

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  • Cite this

    Mock, D. J., Powers, J. M., Goodman, A. D., Blumenthal, S. R., Ergin, N., Baker, J. V., Mattson, D. H., Assouline, J. G., Bergey, E. J., Chen, B., Epstein, L. G., & Blumberg, B. M. (1999). Association of human herpesvirus 6 with the demyelinative lesions of progressive multifocal leukoencephalopathy. Journal of NeuroVirology, 5(4), 363-373. https://doi.org/10.3109/13550289909029477