Canine distemper virus (CDV), a morbillivirus closely related to human measles virus, is a viral pathogen of dogs. Infection in susceptible dogs may lead to demyelinating encephalomyelitis; demyelinating lesions produced are similar to those observed in multiple sclerosis and subacute sclerosing panencephalitis. The overall objective of the proposed research is to utilize CDV infection in gnotobiotic dogs as a model for virus-associated demyelinating encephalitis. Experimental infection of gnotobiotic dogs at 3 weeks of age with R252-CDV results in a high incidence of demyelination. A key feature of the disease at this age is persistent infection within the brain. The disease will be studied in an integrated program involving morphologic pathology, immunology, virology, and neurochemistry. Morphologic studies will be directed toward the pathogenesis of the lesions and in evaluation of various therapeutic measures designed to alter the course and nature of the disease. Immunologic studies will center around autoimmune phenomena (e.g., antimyelin antibodies) and their role in disease, immunotherapy (e.g., transfer factor) and the role of antiviral immunity in persistent neurological disease. Virological studies will center around the unique properties of R252-CDV that may be associated with demyelinating potential, and host-viral interactions in persistent infection in vitro and in vivo. Neurochemical studies are directed toward the biochemical and enzymatic events of the demyelinating process and how these pathways can be altered or subverted with chemotherapy.