Role of host immune response in the development of either encephalitic or paralytic disease after experimental rabies infection in mice.

The clinical and histopathological manifestations of the infection of immunosuppressed (cyclophosphamide-treated) and immunocompetent (control) adult mice with the CVS ts 2 strain of fixed rabies virus were correlated with the kinetics of virus multiplication in the central nervous system and with the development of serum antibody. In immunocompetent mice severe paralytic disease causing 80% mortality was accompanied by marked inflammation and degeneration of the central nervous system parenchymatous tissue. Antirabies antibody was detected in all immunocompetent mice severely paralyzed from postinoculation day 6 on; virus was rarely isolated. In contrast, immunosuppressed mice developed encephalitic symptoms with only minor paralysis; the infection was 100% fatal. Histopathological changes in immunosuppressed mice were confined to degeneration and necrosis of individual neurons and mild microglial reaction; virus was isolated from all of these mice. No significant level of antibody was detected. Similar manifestations were seen after infection of immunodeficient (athymic) mice except that the athymic mice developed levels of antibody similar to those of control mice on day 6; antibodies in athymic mice were predominantly of immunoglobulin class M.