BACKGROUND-MATERIALS: Mice with normal or impaired immune function were studied for responses to intranasal infection with MHV68, a gammaherpesvirus that acutely infects lung epithelial cells and establishes latency in B cells. Infection of normal mice induced a vigorous pulmonary inflammatory response composed of T, B, and NK cells and macrophages and stimulated activation and proliferation of T and B cells in spleen. METHODS-RESULTS- CONCLUSIONS: Resolution of the infection was associated with induction of MHV68-specific antibodies, but virus-specific cytotoxic T cells were not detected. Mice inoculated with retroviruses that induce severe immunodeficiency unexpectedly cleared MHV68 from lung in the same time-frame as controls and failed to develop latency as determined by infectious center tests of spleen cells. In contrast, control of MHV68 infection in spleen and/or lung was impaired in mice deficient in CD4+ or CD8+ T cells or both T cell subsets, B cells, IFN-gamma, or inducible nitric oxide synthase (iNOS). Infection was uniformly lethal in nude and iNOS-deficient mice and killed one-third of IFN-gamma-deficient mice. These results indicate that resistance to MHV68 is markedly influenced by expression of IFN-gamma from T cells leading to induction of iNOS and generation of nitric oxide.
BACKGROUND-MATERIALS: Mice with normal or impaired immune function were studied for responses to intranasal infection with MHV68, a gammaherpesvirus that acutely infects lung epithelial cells and establishes latency in B cells. Infection of normal mice induced a vigorous pulmonary inflammatory response composed of T, B, and NK cells and macrophages and stimulated activation and proliferation of T and B cells in spleen. METHODS-RESULTS- CONCLUSIONS: Resolution of the infection was associated with induction of MHV68-specific antibodies, but virus-specific cytotoxic T cells were not detected. Mice inoculated with retroviruses that induce severe immunodeficiency unexpectedly cleared MHV68 from lung in the same time-frame as controls and failed to develop latency as determined by infectious center tests of spleen cells. In contrast, control of MHV68 infection in spleen and/or lung was impaired in mice deficient in CD4+ or CD8+ T cells or both T cell subsets, B cells, IFN-gamma, or inducible nitric oxide synthase (iNOS). Infection was uniformly lethal in nude and iNOS-deficient mice and killed one-third of IFN-gamma-deficient mice. These results indicate that resistance to MHV68 is markedly influenced by expression of IFN-gamma from T cells leading to induction of iNOS and generation of nitric oxide.
Authors: Christopher H Parsons; Laura A Adang; Jon Overdevest; Christine M O'Connor; J Robert Taylor; David Camerini; Dean H Kedes Journal: J Clin Invest Date: 2006-06-22 Impact factor: 14.808
Authors: Brian S Wakeman; L Steven Johnson; Clinton R Paden; Kathleen S Gray; Herbert W Virgin; Samuel H Speck Journal: J Virol Date: 2014-02-26 Impact factor: 5.103