Immune control and viral countermeasures in murine cytomegalovirus infection

Murine cytomegalovirus (MCMV) is a widely used model for studying β‑herpesvirus infection, eliciting strong CD8 T‑cell responses despite encoding multiple genes that block MHC class I antigen presentation. Although these immune‑evasion genes prevent CD8‑mediated killing in vitro, their importance in immunocompetent hosts remains unclear. This dissertation examined CD8 T‑cell responses and viral loads following infection with wild‑type and mutant MCMV lacking these genes across multiple mouse genetic backgrounds. The findings show that non‑MHC genetic factors influence CD8 immunodominance and that immune‑evasion genes primarily enhance viral replication in the salivary glands of susceptible mice. Under more natural infection conditions, mutant virus was more effectively controlled, suggesting these genes are conserved to support viral transmission rather than acute immune escape. This work highlights the nuanced role of MHC class I evasion in MCMV pathogenesis and refines the utility of current infection models.