Characterization of coronavirus JHM variants isolated from wistar furth rats with a viral-induced demyelinating disease

Murine hepatitis virus (MHV) can cause neurological disease when inoculated intracerebrally (ic) into mice and rats. Specifically the JHM strain of MHV (MHV-JHM) generally causes an acute encephalitis when inoculated is into 2-day-old Wistar Furth rats. In contrast, JHM generally produces a chronic demyelinating disease with resulting posterior paralysis when inoculated is into 10-day-old Wistar Furth rats. In addition, while JHM readily produces a productive infection in a mouse fibroblast cell line (L-2), it does not form syncytia or replicate well in a tissue cell line of glial origin (G26-24). We have isolated and characterized three MHV-JHM viral variants from the central nervous system of two Wistar Furth rats with a MHV-JHM-induced demyelinating disease. The pattern of viral-specific mRNA for all three of these variants differed from what was observed for the wild-type parental MHV-JHM that had been passaged only in tissue culture. One of these variants, ATIIf cord virus, which induced a chronic demyelinating disease in 2- or 10-day-old intracerebrally inoculated Wistar Furth rats, had a deletion in the coding region of the peplomer glycoprotein mRNA. In addition, this variant formed massive syncytia and replicated well in G26-24 cells. We have not detected this deletion in the other two JHM variants, ATIIf brain virus and ATIIe brain virus. ATIIf brain virus and ATIIe brain virus primarily produced an acute encephalitis when reinoculated into 2-or 10-day-old Wistar Furth rats. In addition, these two variants did not form syncytia and had a reduced ability to replicate in G26-24 cells.