The aim of this project is the interdisciplinary study of viral-induced demyelination and persistance. The project will concentrate on host factors in JHM virus infection. JHM is a mouse coronavirus which serves as a useful model to study the many factors by which a virus could play a role in the pathogenesis of multiple sclerosis. JHM produces a persistent infection and chronic demyelination. The genetic background of the host appears to play an important role in susceptibility and the model can be used both in vivo and in vitro to study basic questions of viral-cell interactions in regard to the immune system and the role of specific CNS cells in the establishment and maintenance of chronic infections. Host factors will be studied by (1) defining the genetic influences such as the identification of specific genes and their linkage relationships to known markers which might give a clue to the mechanism of their action, (2) characterizing antiviral antibody, proliferative and cytotoxic T cell responses by using virus-specific T cell clones and by defining the role of NK cells in a chronic process where the virus does not elicit interferon production, (3) utilizing monoclonal antiviral antibody to study antibody-viral interactions at the cell serface with specific reference to the establishment and maintenance of persistent infection, the induction and mechanism of antigenic drift and alterations in the selective vulnerability of CNS celss to chronic infection. The JHM virus-cell interactions will be studied in vivo and in vitro utilizing animals of specific genetic background and extensive tissue culture systems. Genetics, immunologic, virologic, and neurobiologic techniques will be employed in an extensive collaborative effort.
