Characteristics of a murine gammaherpesvirus infection immunocompromised mice.
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.
Kulkarni
A B
AB
Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0760, USA.
Holmes
K L
KL
Fredrickson
T N
TN
Hartley
J W
JW
Morse
H C
HC
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D018142:Gammaherpesvirinae / Q000276:immunology*; D006566:Herpesviridae Infections / Q000276:immunology* / Q000473:pathology; D016867:Immunocompromised Host; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D008171:Lung Diseases / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
D000914:Antibodies, Viral; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase