Mechanisms of demyelination are studied in two virus induced demyelinating diseases in mice by means of electron microscopy, ultrastructural immunolabeling techniques, and assays of cellular and humoral immunity which use infected glial cells in tissue culture as targets. The experimental models are induced by Theiler's murine encephalomyelitis virus (TMEV) or the temperature sensitive mutant 472 of the Chandipura virus (CV). The objectives in studying TMEV are 1) to determine definitively wheter TMEV demyelination is immune mediated by transferring spleen cells from mice during the development of the white matter lesion and searching for histologic lesions in recipient mice, using as positive controls the transfer of lymphoid cells from mice afflicted with experimental autoimmune encephalomyelitis, 2) to determine if demyelination is the result of an autoimmune process directed against myelin by desensitizing mice with myelin components prior to infection with TMEV, 3) to determine if demyelination is caused by neutral proteases released by macrophages by attempting to prevent demyelination with neutral protease inhibitors and macrophage depletion, 4) to determine if demyelination is caused by an immune response directed against persistently infected oligodendroglial cells by using persistently infected primary glial cultures as targets to study lymphocytotoxicity. The objectives in studying the demyelination associated with infective Chandipura virus are to determine 1) the ultrastructural morphologic features of demyelination, 2) the ultrastructural characteristics of the cells infected during various stages of infection, 3) ultrastructural evidence of viral antigens expressed on the surface of infected cells by using monospecific antibodies to the structural proteins of TS472CV as probes to label antigens. The findings are expected to contribute to the understanding of human demyelinating diseases, such as multiple sclerosis.
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