IFI16 and infection: To counteract this restriction activity, the tegument protein pUL83/pp65, in the early phase of infection, hijacks IFI16 to activate the major immediate–early promoter–enhancer (MIEP) expression, whereas later during infection, pUL83/pp65 interacts with IFI16 at the promoter of the UL54 gene and downregulates viral replication, as shown by using a HCMV mutant-lacking pUL83/pp65 expression [114].