Document Detail

Human herpesvirus type 6 indirectly enhances oligodendrocyte cell death.
MedLine Citation:
PMID:  13129768     Owner:  NLM     Status:  MEDLINE    
Accumulating evidence suggests that human herpesvirus type 6 (HHV-6) plays a pathogenic role in diseases of the central nervous system including multiple sclerosis (MS). Recent studies have indicated that HHV-6 DNA is detected with high frequency in MS lesions compared to normal-appearing white matter, implicating a role for HHV-6 in MS pathogenesis. It appears that T cells, which infiltrate into the brain in MS patients, and resident oligodendrocytes harbor HHV-6 virus in MS lesions. Because T cells infected with HHV-6 have elevated proinflammatory gene expression, we hypothesized that HHV-6 could be indirectly cytotoxic to glial cells, including oligodendrocytes. Supernatants from SupT1 cells infected with HHV-6 variant A (GS or U1102) or variant B (Z29) significantly reduced MO3.1 cell proliferation by 75% +/- 10%, 78% +/- 8% or 51% +/- 9%, respectively. HHV-6 viral supernatants (GS or U1102 or Z29) significantly increased MO3.1 or primary human oligodendrocyte precursor cells (OPCs) cell death, whereas primary human fetal astrocytes were not affected. Removal of HHV-6 virions or proteins by trypsin treatment from culture supernatants did not reverse the loss in oligodendrocyte proliferation or viability. Supernatants from HHV-6 GS or U1102 cultures were significantly more cytotoxic to MO3.1 cells or OPCs compared to supernatants from T cells infected with Z29. Dying oligodendrocytes did not have an apoptotic-like phenotype and toxicity was not inhibited by general inhibitor of apoptosis, ZVAD. Further, oligodendrocytes had minimal caspase-3 activation even in the presence of staurosporine, suggesting that cell death followed caspase-independent pathways. These results indicate that HHV-6 is indirectly cytotoxic to oligodendrocytes and that cell death is driven primarily by caspase-independent pathways.
Hong Kong; Quinton Baerbig; Laine Duncan; Nick Shepel; Michael Mayne
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neurovirology     Volume:  9     ISSN:  1355-0284     ISO Abbreviation:  J. Neurovirol.     Publication Date:  2003 Oct 
Date Detail:
Created Date:  2003-09-17     Completed Date:  2003-12-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9508123     Medline TA:  J Neurovirol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  539-50     Citation Subset:  IM    
Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada.
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MeSH Terms
Brain / pathology*
Cell Death
Cell Line
Cell Survival
Cells, Cultured
Cytotoxicity, Immunologic
Fluorescent Antibody Technique
Herpesvirus 6, Human* / genetics,  isolation & purification
Oligodendroglia / pathology*
Polymerase Chain Reaction
Roseolovirus Infections / diagnosis,  immunology,  pathology*
T-Lymphocytes / immunology

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