Replication of mouse hepatitis viruses with high and low virulence in cultured hepatocytes

Ten strains of mouse hepatitis virus with different levels of virulence and hepatotropism were examined for the ability to replicate in cultured mouse hepatocytes. All of these viruses multiplied well in hepatocytes, attaining a maximum of 10(5) to 10(7) PFU per 0.2 ml, with cytopathic effects characterized by the formation of polykaryocytes. However, in nonparenchymal adherent cells of the liver (liver macrophages), highly virulent mouse hepatitis virus type 2 multiplied to a titer 1,000 times higher than that of mouse hepatitis virus S with a low virulence. These results suggest that the virulence of mouse hepatitis virus in infected mice is determined by its potential for replication not in hepatocytes, but in macrophages, including Kupffer cells in the liver.