Effect of a retroviral immunodeficiency syndrome on resistance to MCMV: a role for natural killer cells.

Mice exhibiting T cell immunodeficiency and lymphadenopathy induced by LP-BM5 MuLV (MAIDS) were assessed for their ability to control murine cytomegalovirus (MCMV) infection. Elevated replication of MCMV was observed in spleens 4-6 days after MCMV infection. Production of interferon alpha/beta in response to MCMV was abrogated by MAIDS and natural killer (NK) cell activity, assessed by lysis of YAC-1 target cells, was correspondingly depressed on Day 1. However, this was elevated at later times. As previous studies attribute early control of MCMV in C57BL mice with splenic NK1.1 cells, we confirmed that YAC-1 lysis declines and MCMV titres are elevated in M- mice given antibodies to NK1.1 or asialo GM1. However, M+ mice were less severely affected by these regimes. Hence M+ mice may acquire cells that do not express NK1.1 or asialo GM1, but are able to lyse YAC-1 target cells and partially control MCMV replication. MCMV was essentially cleared from the spleens and livers of M+ and M- mice by Day 11, but in the salivary gland MCMV replication was enhanced by MAIDS 11-30 days postinfection. The role of CD4 T cells in this phenomenon is being investigated. Since patients with acquired immunodeficiency syndrome exhibit suppressed T and NK cell activity and experience severe cytomegalovirus disease, the model warrants further study.