Journal article
The HHV6 paradox: ubiquitous commensal or insidious pathogen? A two-step in situ PCR approach
Journal of clinical virology, Vol.16(3), pp.159-178
2000
DOI: 10.1016/S1386-6532(99)00084-0
PMID: 10738136
Abstract
Background: Progressive multifocal leukoencephalopathy (PML) and multiple sclerosis (MS) are demyelinative diseases of the central nervous system (CNS). PML occurs mostly in individuals with AIDS-impaired immunity and is thought to be caused by JC polyoma virus (JCV). In MS a neurotrophic virus trigger is suspected, but the precise etiology remains unknown. Human herpesvirus 6 (HHV6) is a ubiquitous, commensal and usually benign beta-herpesvirus. Some researchers have found evidence for HHV6 infection in MS plaques and sera. We recently demonstrated a high frequency of cells containing HHV6 genome in PML lesions, as well as co-infection of oligodendrocytes by JCV and HHV6. This suggests that HHV6 may be a co-factor in the etiology of PML, and raises questions about its role in other demyelinative diseases.
Objectives: To determine the prevalence and cellular localization of HHV6, JCV and HIV-1 infected cells in PML, MS, AIDS and control CNS tissues, and their potential relationship with disease.
Study design: An unconventional, sensitive two-step in situ polymerase chain reaction (ISPCR) procedure was used to amplify and detect HHV6, JCV and HIV-1 genomic DNAs in formalin fixed, paraffin-embedded archival CNS tissues. HHV6, JCV and HIV-1 gene expression was detected by ICC for HHV6 p41 and gp101, JCV large T, and HIV-1 p24
gag and NEF proteins.
Results: A high frequency of HHV6 genome was consistently detected in both PML and MS white matter lesional cells; a peri-lesional concentration was notable. HHV6 was found mainly in oligodendrocytes, but neurons were also infected. HHV6 was present in larger amounts than JCV in PML lesions, while more HIV-1 than HHV6 was present in AIDS. Variable amounts of HHV6 genome were detected in normal, AIDS and other control brains; the frequency of infected cells tended to increase with patient age.
Conclusions: High concentrations of HHV6 genome in association with PML and MS lesions, open the possibility that HHV6 activation may play a role in the pathogenesis of these demyelinative diseases.
Details
- Title: Subtitle
- The HHV6 paradox: ubiquitous commensal or insidious pathogen? A two-step in situ PCR approach
- Creators
- Benjamin M Blumberg - VA Bio-Medical Research Institute, Building 7, East Orange VA Medical Center, 385 Tremont Avenue, East Orange, NJ 07018, USADavid J Mock - Department of Medicine/Infectious Diseases, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USAJames M Powers - Department of Pathology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USAMasumi Ito - Department of Pathology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USAJose G Assouline - Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USAJeffrey V Baker - Department of Neurology, University of Rochester School of Medicine and Dentistry, Box 605, 601 Elmwood Avenue, Rochester, NY 14642, USABojun Chen - Department of Neurology, University of Rochester School of Medicine and Dentistry, Box 605, 601 Elmwood Avenue, Rochester, NY 14642, USAAndrew D Goodman - Department of Neurology, University of Rochester School of Medicine and Dentistry, Box 605, 601 Elmwood Avenue, Rochester, NY 14642, USA
- Resource Type
- Journal article
- Publication Details
- Journal of clinical virology, Vol.16(3), pp.159-178
- DOI
- 10.1016/S1386-6532(99)00084-0
- PMID
- 10738136
- NLM abbreviation
- J Clin Virol
- ISSN
- 1386-6532
- eISSN
- 1873-5967
- Publisher
- Elsevier B.V
- Language
- English
- Date published
- 2000
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Iowa Neuroscience Institute; Urology
- Record Identifier
- 9984070670302771
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