Immune control of primary infection vs reactivation. Primary CMV infection induces activation of DC subsets to secrete type I IFNs (IFNα/β), which have antiviral properties, and, in combination with IL-12 and -18, activate NK cells and promote Th1 and Tc1 differentiation of naive CD4⁺ and CD8⁺ T cells. NK cells recognize MCMV-infected cells, and engagement of activating NK cell receptors induces cytokine and cytolytic pathways. Conventional T cells secrete antiviral cytokines (IFNγ) and cytolytic granules (perforin, pfn; granzymes, gzm) to lyse infected cells. During chronic infection, virus replication is sustained in the salivary gland to favor horizontal viral transmission; in this organ virus is controlled principally by CD4⁺ T cells. During latency, CMV is restrained by coordinated adaptive immune responses, involving both T cells and antibodies derived from memory B cells and plasma cells. Memory NK cells may also be relevant in this setting. Reactivation ensues when antiviral T-cell and humoral responses are lost or concurrently suppressed.