Hepatitogenicity of three plaque purified mutants of hepatotropic mouse hepatitis virus, MHV-2.

Hepatitogenicity of three plaque purified mutant strains of mouse hepatitis virus, designated as MHV-2S, -2M and -2L, isolated from MHV-2 infected SR-CDF1-DBT cells was studied. After intraperitoneal inoculation with 2 x 10(5) PFU of parental MHV-2 and its mutants to 4-week-old female ICR mice, 40% of mice inoculated with MHV-2S and 20% of mice with -2M died in one week, whereas with -2L all mice survived. All mice inoculated with MHV-2 died in 3 days postinoculation (p.i.). Virus titer of the liver of mice inoculated with MHV-2, -2S and -2M reached peaks (MHV-2:10(7) PFU/0.2 g, -2S: 10(5) PFU/0.2 g and -2M: 10(6) PFU/0.2 g) at 96 hr p.i., while with -2L a peak titer (10(3) PFU/0.2 g) was shown at 48 hr p.i. Immunofluorescence revealed MHV specific antigen in the liver of MHV-2S infected mice in and around necrotic areas though less extensive than that of parental MHV-2 infected mice. With MHV-2M specific fluorescence was restricted in degenerated hepatocytes in the small necrotic foci. In mice inoculated with MHV-2L only faint fluorescence was detected. Histopathologically, in the liver of MHV-2S infected mice zonal necrosis and cell infiltration were observed. There were spotty necrosis and focal cell infiltration in the liver of MHV-2M infected mice and only small inflammatory foci were seen in MHV-2L infected mice. Large number of extracellular virions were detectable in MHV-2S but not in -2M and -2L infected mice by electron microscopy.