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The replication of the murine coronavirus MHV (mouse hepatitis virus) and the molecular and genetic basis of its interactions with the host are being studied. Coronaviruses are important human pathogens causing a broad range of diseases depending on the particular virus and host system examined. Human diseases associated with coronaviruses include SARS (severe acute respiratory syndrome), less severe lower and upper respiratory disease, and gastroenteritis. MHV produces a broad spectrum of disease in the mouse, and provides excellent small animal models for hepatitis, for SARS, and for multiple sclerosis.We have two projects in the laboratory. In collaboration with investigators in Toronto and Pennsylvania my laboratory has developed a MHV model for SARS. We are currently developing genetic tools to allow us to determine the role of various coronavirus proteins in the pathogenesis of SARS. The second project is focused on understanding how cis-acting sequences at the 5' and 3' untranslated regions (UTRs) function in replication. We have developed a novel model of structure of the 5'UTR and we are examining the role of the individual RNA stem-loop structures predicted by this model in viral replication using biochemical, cell biologic, and reverse genetic approaches.
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