MHV Neuropathogenesis: The Study of Chimeric S Genes and Mutations in the Hypervariable Region
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Mouse hepatitis virus (MHV) is studied as a model system for both acute and chronic virus-induced neurologic disease. Infection of susceptible mice with MHV results in a potentially fatal acute encephalomyelitis, and survivors of this acute disease often go on to develop a chronic demyelinating disease. Using targeted recombination we have demonstrated that the MHV spike (S) glycoprotein is a major determinant of the severity of the acute disease (Phillips et al., 1999). Isogenic recombinant viruses differing exclusively in the spike gene were found to differ dramatically in their neurovirulence. Recombinants containing the spike of the highly neurovirulent MHV-4 virus were highly neurovirulent while recombinants containing the spike of the mildly neurovirulent MHV-A59 virus exhibited a similarly mild degree of neurovirulence.