During human cytomegalovirus (HCMV) infection, ISGs like viperin, ISG15, IFIT1/2/3, and Mx1/2 are upregulated in an IRF3-dependent but a STAT1-independent manner (110), potentially through its immediate early gene 1 (IE1) protein (111) or a distinct ISRE-recognizing complex involving histone acetyltransferase CBP and IRF3, which is triggered by viral entry without requiring genome replication (112). The gene discussed is IRF3; the disease is cytomegalovirus infection.