Mouse hepatitis virus A59-induced demyelination can occur in the absence of CD8+ T cells.
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.
Gombold
J L
JL
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia 19104-6076, USA.
Sutherland
R M
RM
Lavi
E
E
Paterson
Y
Y
Weiss
S R
SR
D000818:Animals; D001921:Brain / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003711:Demyelinating Diseases / Q000209:etiology* / Q000276:immunology / Q000821:virology; D005260:Female; D017353:Gene Deletion; D005805:Genes, MHC Class I; D007111:Immunity, Cellular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D006517:Murine hepatitis virus / Q000472:pathogenicity*; D013116:Spinal Cord / Q000473:pathology / Q000821:virology; D001613:beta 2-Microglobulin / Q000235:genetics
D001613:beta 2-Microglobulin