Effect of a retroviral immunodeficiency syndrome on murine cytomegalovirus-induced hepatitis

We have studied the effects of LP-BM5 MuLV-induced murine acquired immunodeficiency syndrome (MAIDS) on concomitant murine cytomegalovirus (MCMV) infection in the livers of C57BL mice. A delayed inflammatory response in livers of mice with MAIDS (M⁺) on day 4 was associated with impaired clearance of MCMV-infected cells 6 days after infection. This correlated with increased levels of inflammation and serum alanine transaminase. The latter reflects enhanced hepatic necrosis, which was evident histologically, Delayed-type hypersensitivity responses to MCMV antigen were unimpaired in M⁺ mice and were mediated by CD8⁺ cells. Depletion of NK1.1⁺ cells front M+ mice increased MCMV replication and associated liver damage on day 6, whereas CD8⁺ depletion had little effect. In contrast, in the presence of CD8⁺ cells M^- C57BL mice did not require NK1.1⁺ cells for control of hepatic MCMV infection, but dual NK1.1⁺ and CD8⁺ depletion dramatically potentiated hepatic MCMV replication. Our results suggest that M⁺ mice may acquire non-NK1.1⁺ and non-CD8⁺ cells that are able to partially control hepatic MCMV infection. These findings are discussed with reference to mortality in M⁺ mice after high-dose MCMV infection, as this is initially delayed but ultimately higher than in M^- controls.