- Brain Awareness Week
Localization of virus and cell-mediated immune response in mice developing demyelination after infection with mouse hepatitis virus
My laboratory has been interested in the pathogenesis of murine coronavirus infections for several years. Now, we will also study three respiratory human coronavirus infections: SARS-coronavirus, human coronavirus-OC43 and human coronavirus-NL63.
Mice infected with mouse hepatitis virus develop a demyelinating disease with many similarities to the human disease, multiple sclerosis. Research in my laboratory is aimed at determining the immunological and viral factors involved in the demyelinating process. Previously, we determined the CD4 and CD8 T cell epitopes recognized in the central nervous system (CNS) of infected mice. We showed that in mice infected chronically with the virus, cytotoxic T cell escape mutants arise. These mutations completely abrogate recognition by CD8 T cells and thereby facilitate persistence. We have developed a reverse genetics system for introducing mutations into the murine coronavirus genome. We have developed a model to determine the role of individual effector molecules in demyelination, using immunodeficient mice infected with the virus. The ultimate goal of these experiments is to develop a system whereby we can introduce changes into immunologically important epitopes within the virus and study the effects of these changes on virus replication and persistence in the infected CNS.
The SARS-coronavirus causes the most significant disease of any of the human coronaviruses. Our goal is to understand the mechanism of disease. For this purpose, we are developing animal models of SARS. We are also analyzing individual OC43 and NL63 proteins for their roles in pathogenesis, both as isolated proteins and in the context of infectious, recombinant viruses.