MOUSE HEPATITIS-VIRUS A59-INDUCED DEMYELINATION CAN OCCUR IN THE ABSENCE OF CD8(-CELLS() T)

Mouse hepatitis virus causes a chronic demyelinating disease in C57BL/ 6 mice. While early studies suggested demyelination is due to direct c ytolytic effects of virus on oligodendrocytes, there is increasing evi dence for the involvement of the immune system in the mechanism of dem yelination. In this study we have asked whether demyelination can occu r in the absence of functional MHC class I expression and CD8(+) T cel ls. We infected transgenic mice lacking expression of beta(2) microglo bulin (beta(2)M(-/-) mice) with MHV-A59. In beta(2)M(-/-) mice, virus was much more lethal than in either of the parental strains used to pr oduce the mice; furthermore, while clearance from the CNS did occur in beta(2)M(-/-) mice, it was slower than in C57BL/6 mice. This is consi stent with the importance of CD8(+) cells in viral clearance. Because of the increased sensitivity of the beta(2)M(-/-) mice to infection, o nly low levels of virus could be used to evaluate chronic disease. Eve n at these low levels, demyelination did occur in some animals. To com pare infection in beta(2)M(-/-) and C57BL/6 mice we used a higher dose of an attenuated variant of MHV-A59, C12. The attenuated variant indu ced less demyelination in C57BL/6 mice compared to wild type A59, but the levels observed were not significantly different from those seen i n beta(2)M(-/-) mice. Thus, MHV-induced demyelination can occur in som e animals in the absence of MHC class I and CD8(+) cells.