Interactions between the immune system and murine hepatitis virus strain A59: Local environmental requirements, resultant CNS pathology, and lytic effector cells

Murine hepatitis virus (MHV) A59 infects both the liver and the CNS after intracerebral infection in mice. Viral infection is characteristically followed by the development of CNS demyelination similar to that seen in humans suffering from multiple sclerosis. In this thesis we explored the interactions between the immune response and the virus. Experiments in B cell and antibody deficient mice revealed that antibodies are crucial for clearance of virus from the CNS but not from the liver. Although antibodies appear to be present and functional in the control of virus in the CNS at the time of demyelination, we could find no evidence that antibodies contribute to demyelination. On the contrary, we found the MHV-A59 could induce demyelination not only in the absence of B cells but also in the concurrent absence of T cells. Studies of the lytic immune response to MHV-A59 suggest that there may be multiple lytic effector cell populations, although positive identification of these cells and clarification of their potential role in demyelination have yet to be obtained. Further understanding of the interactions between MHV and the immune system in the CNS will hopefully lead to improvements in our understanding of how demyelination occurs and where interventions may be effective