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Association of human herpesvirus 6 with the demyelinative lesions of progressive multifocal leukoencephalopathy
D J Mock1, J M Powers, A D Goodman
1Department of Medicine/Infectious Diseases, University of Rochester School of Medicine and Dentistry, NY 14642, USA.
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 ofPML. 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.
Insights
Human herpesvirus-6 (HHV6) activation, alongside JC virus, is linked to demyelinating lesions in Progressive Multifocal Leukoencephalopathy (PML). This study found HHV6 DNA and antigens predominantly in oligodendrocytes within PML lesions.
Area of Science:
- Neurovirology
- Immunology
- Neuropathology
Background:
- Progressive Multifocal Leukoencephalopathy (PML) is a severe demyelinating disease of the central nervous system.
- PML predominantly affects individuals with compromised cell-mediated immunity.
- JC polyoma virus is the established etiological agent of PML.
Purpose of the Study:
- To investigate the potential role of human herpesvirus-6 (HHV6) in the pathogenesis of PML.
- To determine the presence and location of HHV6 in brain tissues affected by PML.
Main Methods:
- Utilized a two-step in-situ polymerase chain reaction (PCR) to detect HHV6 genomic DNA in archival brain tissues.
- Employed immunocytochemistry to identify HHV6 antigens within affected cells.
- Performed double immunohistochemical staining to co-localize HHV6 and JC virus (JCV) large T antigen.
Main Results:
- High frequency of HHV6 genome detected in oligodendrocytes within and surrounding PML demyelinative lesions.
- Active HHV6 infection, indicated by antigen presence, was confined to swollen oligodendrocytes within PML lesions.
- Co-labeling of JCV large T antigen and HHV6 antigens observed in oligodendrocytes within PML lesions.
- Lesser amounts of HHV6 detected in control tissues, with no detectable antigens in HIV-1 encephalopathy without PML.
Conclusions:
- HHV6 activation appears to be associated with PML pathogenesis.
- The findings suggest a potential co-factor role for HHV6 in JC virus-induced demyelination.
- Further research is warranted to elucidate the precise mechanisms of HHV6 involvement in PML.