PRR activation and signaling (including TLR7, TLR9, AIM2, and cGAS-STING) induces proinflammatory cytokine production by myeloid cells (antiviral wave 1). IL-12 production by cDC1s in turn stimulates secretion of protective ILC1-derived IFN-γ (antiviral wave 2). These first two waves are initiated in tissue at the site of viral entry. Myeloid cell-derived IL-12 and IL-18 also trigger IFN-γ production by NK cells, and type 1 IFNs enhance NK cell cytotoxicity. Along with Ly49H engaging MCMV-encoded m157 on infected cells, IL-12, type 1 IFN, and costimulatory signals synergize to drive prolific clonal expansion of Ly49H+ NK cells (antiviral wave 3) as MCMV disseminates. During this time, an antigen-specific T cell response, dependent on the canonical three signals (TCR, costimulation, and proinflammatory cytokines), begins to develop against MCMV to keep the virus in latency (antiviral wave 4). Colored bars span the duration of a given cellular response, with the color saturation representing the magnitude of the response (or viral burden in peripheral blood) at that time.