Counteracts the host antiviral immune response when activated and phosphorylated, by preventing host IRF3 from entering the nucleus (PubMed:15452220). Inhibits also the type I interferon production by inactivating the enzymatic activity of DNA sensor CGAS without affecting STING1 (PubMed:29263269). Participates in the transactivation of viral major immediate-early genes by the recruitment of host IFI16 to the promoters pf these genes (PubMed:20504932). Interacts with host NCL/nucleolin (PubMed:21053310). Interacts with host IFI16 (PubMed:20504932). Interacts with host CGAS; this interaction inhibits CGAS enzymatic activity (PubMed:29263269). As part of the incoming virion, pp65 is targeted to the nucleus immediately after infection (PubMed:7815485). The newly synthesized pp65 is observed in the nucleus until some time after 48 hours postinfection (PubMed:17715235). Thereafter, pp65 is probably exported and accumulates in the cytoplasm (PubMed:17715235). Also found in dense bodies (PubMed:7815485). Phosphorylation may play a role in the localization of the protein. Belongs to the herpesviridae pp65 family.