The pathogenesis of MHV nucleocapsid gene chimeric viruses.

A set of viruses in which various segments of the nucleocapsid (N) gene of MHV have been substituted with the corresponding segments of bovine coronavirus (BCV) by targeted recombination were analyzed for their biologic properties. Histology for organ pathology and plaque assay for viral titer analysis following intracerebral (IC) inoculation were studied. One chimeric virus (Alb85), in which only a small segment of the N gene was replaced, exhibited a phenotype similar to wild type MHV-A59. However, three of the chimeric viruses (Alb106, Alb112 and Alb100) produced acute encephalitis and demyelination but without hepatitis following IC inoculation. Intravenous (IV) and intrahepatic (IH) inoculations were able to restore the ability of these viruses to produce hepatitis. The common denominator of the three chimeric viruses with a different phenotype is a region between aa 306 and aa 386 in which 17 amino acids (aa) differences exist between the two strains. Thus this region may contain determinants which enable the virus to exit the brain and reach the blood stream.