GAMMA-INTERFERON IS NOT ESSENTIAL FOR RECOVERY FROM ACUTE INFECTION WITH MURINE GAMMAHERPESVIRUS-68

Murine gammaherpesvirus 68 (MHV-68) when administered intranasally ind uces high levels of gamma interferon (IFN-gamma) in the lymphoid tissu es of infected mice, In order to investigate the role of this cytokine in the immune response to MHV-68, mice which were congenitally defici ent in the IFN-gamma gene (IFN-gamma knockout mice) were infected with the virus, Comparison of the courses of the disease in wild-type cont rol and IFN-gamma knockout mice revealed surprisingly little differenc e. Both groups of mice had cleared infectious virus from the lungs 15 days after infection, although there did appear to be a slight delay i n viral clearance in the IFN-gamma knockout mice, In addition, after t he initial phase of viral clearance, the lungs of both groups remained clear of replicating virus throughout the course of the experiment, w hich concluded 34 days after infection, Consistent with these observat ions, cytotoxic T-cell activities were similar in the two groups of mi ce, Levels of latent virus were comparable in wild-type and knockout m ice over the time course studied, Furthermore, analysis of the numbers , types, and activation status of cells in the lungs, lymph nodes, and spleens of control and knockout mice revealed no striking difference, This suggests that IFN-gamma is not essential for regulating the cell recruitment or proliferation that normally occurs during this viral i nfection, Apart from the expected lack of IFN-gamma, cytokine profiles were not dramatically altered in IFN-gamma knockout mice, demonstrati ng that IFN-gamma did not suppress the proliferation or differentiatio n of Th2 cells during MHV-68 infection,These observations indicate tha t IFN-gamma plays a nonessential or redundant role in the control of a cute infection with MHV-68.