Antiviral activity of interferon gamma in vivo during mouse hepatitis virus infection

A/J mice became resistant to experimental MHV3 infection after immunization with UV-inactivated MHV3 (0% mortality, 0/10). Depletion of interferon (IFN) gamma-producing CD4+ T lymphocytes with monoclonal antibodies to CD4+ led to susceptibility to virus infection (60% of mortality, 6/10). The resistance to MHV3 infection of CD4+ T lymphocyte-depleted-A/J mice was restored by treatment with 1000 U of IFN gamma on days -1, 0, 1, 2, 3 and 4 (10% of mortality, 1/10). The low virus titers observed in resistant mice (controls or CD4+ depleted plus IFN gamma treated) were cleared 6 days after infection and the virus titers observed among susceptible mice (CD4+ depleted) increased gradually and peaked on day 6, when the animals died. Previous data, taken together with the direct evidence presented in this paper, provide strong evidence supporting the concept of an in vivo antiviral role of IFN gamma through a central action on the mechanisms of resistance to MHV3 infection.