The pattern of induction of apoptosis during infection with MHV-3 correlates with strain variation in resistance and susceptibility to lethal hepatitis.

In the present study we have investigated the possibility that strain specific differences in the induction of apoptosis in macrophages could play a role in the resistance of strain A/J mice to MHV-3 induced hepatitis. MHV-3 infected macrophages from Balb/c and A/J mice were analyzed at various time points after infection. Apoptosis in A/J macrophages could be detected at 8 h post infection and increased significantly by 12 h, when almost 50-70% of the infected cells were undergoing apoptosis. In Balb/c macrophages, apoptotic changes were less pronounced and were observed in only 5-10% of the cells. MHV-3 induced apoptosis was inversely correlated with the ability of this virus to induce expression of fgl-2 prothrombinase protein and syncytia formation. Infected macrophages from A/J mice did not express fgl-2 protein and did not form syncytia. In contrast, infection of Balb/c derived macrophages resulted in fgl-2 expression and extensive syncytia formation. These data fit a model in which apoptosis of virally infected cells is a protective response which eliminates cells whose survival might be harmful for the whole organism.