Genetic resistance to lethal flavivrus encephalitis. II. Effect of immunosuppression

Abstract

Genetic resistance of C3H/RV mice to lethal infection with Banzi virus (flavivirus) was severely compromised by immunosuppression with cyclophosphamide, sublethal X-irradiation, or thymus (T-) cell depletion. The mortality rate among immunosuppressed mice was usually 100%, but average survival times were shorter for mice treated with cyclophosphamide or for X-irradiated mice (10 days) than for T-cell-depleted mice (17 days). Mice treated with cyclophosphamide had high titers of virus in brain, lymphoid tissues, pancreas, and serum. Viral antigen was widespread in brain and pancreas, and mice developed nonsuppurative meningoencephalitis and pancreatitis. Yields of virus, spread of viral antigen, and lesions in T-cell-depleted mice were similar but less severe. Mice treated with cyclophosphamide did not have detectable hemagglutination-inhibiting antibody. T-cell-depleted mice developed hemagglutination-inhibiting antibody but were not protected from lethal infection. These results indicate that genetic resistance of C3H/RV mice to Banzi virus requires immunological factors, and that T-cells play a significant role in resistance to infection with Banzi virus.