       Document 0263
 DOCN  M9610263
 TI    Mouse hepatitis virus A59-induced demyelination can occur in the absence
       of CD8+ T cells.
 DT    9601
 AU    Gombold JL; Sutherland RM; Lavi E; Paterson Y; Weiss SR; Department of
       Microbiology, University of Pennsylvania School of; Medicine,
       Philadelphia 19104-6076, USA.
 SO    Microb Pathog. 1995 Mar;18(3):211-21. Unique Identifier : AIDSLINE
       MED/96002208
 AB    Mouse hepatitis virus causes a chronic demyelinating disease in C57BL/6
       mice. While early studies suggested demyelination is due to direct
       cytolytic effects of virus on oligodendrocytes, there is increasing
       evidence for the involvement of the immune system in the mechanism of
       demyelination. In this study we have asked whether demyelination can
       occur in the absence of functional MHC class I expression and CD8+ T
       cells. We infected transgenic mice lacking expression of beta 2
       microglobulin (beta 2 M -/- mice) with MHV-A59. In beta 2M-/- mice,
       virus was much more lethal than in either of the parental strains used
       to produce the mice; furthermore, while clearance from the CNS did occur
       in beta 2M-/- mice, it was slower than in C57BL/6 mice. This is
       consistent with the importance of CD8+ cells in viral clearance. Because
       of the increased sensitivity of the beta 2M-/- mice to infection, only
       low levels of virus could be used to evaluate chronic disease. Even at
       these low levels, demyelination did occur in some animals. To compare
       infection in beta 2M-/- and C57BL/6 mice we used a higher dose of an
       attenuated variant of MHV-A59, C12. The attenuated variant induced less
       demyelination in C57BL/6 mice compared to wild type A59, but the levels
       observed were not significantly different from those seen in beta 2M-/-
       mice. Thus, MHV-induced demyelination can occur in some animals in the
       absence of MHC class I and CD8+ cells.
 DE    beta 2-Microglobulin/GENETICS  Animal  Brain/VIROLOGY  CD8-Positive
       T-Lymphocytes/*IMMUNOLOGY  Demyelinating
       Diseases/*ETIOLOGY/IMMUNOLOGY/VIROLOGY  Female  Gastroenteritis Virus,
       Murine/*PATHOGENICITY  Gene Deletion  Genes, MHC Class I  Immunity,
       Cellular  Male  Mice  Mice, Inbred C57BL  Mice, Transgenic  Spinal
       Cord/PATHOLOGY/VIROLOGY  Support, Non-U.S. Gov't  Support, U.S. Gov't,
       P.H.S.  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

