Murine coronavirus spike protein determines the ability of the virus to replicate in the liver and cause hepatitis

Recombinant mouse hepatitis viruses (MHV) differing only in the spike gene, containing A59, MHV-4, and MHV-2 spike genes in the background of the A59 genome, were compared for their ability to replicate in the liver and induc e hepatitis in weanling C57BL/6 mice infected with 500 PFU of each virus by intrahepatic injection. Penn98-1, expressing the MHV-2 spike gene, replica ted to high titer in the liver, similar to MHV-2, and induced severe hepati tis with extensive hepatocellular necrosis. S(A59)R13, expressing the A59 s pike gene, replicated to a somewhat lower titer and induced moderate to sev ere hepatitis with zonal necrosis, similar to MW-A59. S(4)R21, expressing t he MHV-4 spike gene, replicated to a minimal extent and induced few if any pathological changes, similar to MHV-4. Thus, the extent of replication and the degree of hepatitis in the liver induced by these recombinant viruses were determined largely by the spike protein.