Mouse hepatitis virus type 4 (JHM strains). induced fatal central nervous system disease. I. genetic control and murine neuron as the susceptible site of disease

MHV-4 replicates in the neurons of susceptible mice ( Fig. 1; and Tables IV and V) . To do these studies, we utilized methods permitting critical assessment of various (Table III) , showing that virus could replicate there. When MHV-4 was used to infect cultured primary neuronal cells harvested from SJL/J mice, no infectious virus was detected in supernatant fluids. In contrast, cultured neuronal cells from several strains of susceptible mice made 4 to 7 logs of infectious virus. Hence, both in vivo and in vitro studies suggest that the majority of infectious virus found in brains of SJL/J mice after intracerebral inoculation of MHV-4 may reflect replication of virus in nonneuronal cells. This failure to replicate MHV in neurons is manifested as a low incidence of death after one exposes SJL/J mice to MHV-4. However, this restriction is not absolute, because larger doses of virus (an additional 2-3 logs) result in viral replication in their neurons in vivo and death. The stage of replication at which MHV is restricted in neurons is not clear. Studies with neurons and macrophages suggest that the block may take place in some cells after virus-receptor interaction and after some viral antigens are produced. Whether all the viral antigens are made satisfactorily in such cells, or the defect is in packaging and/or release is under investigation.