SUMMARYPeritoneal macrophages were used to analyse host genetic control of mouse hepatitis virus type 4 (MHV-4) infection. Both infectious centre and immunofluorescence assays indicated that only a subset of macrophages from either susceptible (BALB, C3H or C57BL/6J) or resistant (SJL/J) mice were initially infected with MHV-4 during the first cycle of infection. However, compared to macrophages from susceptible mice, three-to sixfold fewer SJL/J macrophages were infected, and there was no amplification of virus replication by involvement of adjacent cells during the second cycle of infection. Treatment of macrophages from susceptible mice with interferon beta could not duplicate the aborted second cycle of infection that occurred in macrophages from resistant mice.

Mouse hepatitis virus type 4 infection of primary glial cultures, which consisted principally of astrocytes (marked by glial fibrillary acidic protein) from encephalitis-susceptible BALB/c or F1 (BALB/c x SJL/J) hybrid mice and resistant SJL/J mice, was studied. Primary neuron cultures from BALB/c and F1 hybrid mice were previously shown to be permissive and were destroyed within 5 days by infection with mouse hepatitis virus type 4, whereas neurons from SJL/J mice were fully resistant. In contrast, in the present study a chronic infection was established and maintained for up to 18 days in glial cultures from all three mouse strains. Infected SJL/J mouse glial cultures produced 10to 50-fold less infectious virus and showed less cytopathic effect than did cultures from either infected BALB/c or F1 hybrid mice. Cytopathic effect was evident initially in cells from all three strains, and continued virus production occurred in the presence of limited additional cytopathic effect. These results were not due to the production of detectable levels of interferon. This study showed that SJL/J mouse primary glial cultures were permissive for mouse hepatitis virus type 4 infection whereas SJL/J primary neuron cultures were not, and that there was an early lytic phase of infection followed by chronic infection in all three strains.