(A) Upon HCMV fusion and content delivery to the infected cell, the tegument protein pp71 binds to and induces the degradation of Daxx (1). This de-represses the viral MIEP and promotes the expression of the IE genes (2). IE1 disrupts the remaining PML-NB proteins by preventing/disrupting the SUMOylation status of PML, and possibly Sp100, further increasing IE gene expression (3). Both IE1 and IE2 negate the effect of HDACs by binding to and sequestering them away from viral promoters (4). Finally, the IE proteins can recruit BTM and TFs to early and late viral promoters to activate their respective genes (5). (B) Upon HSV-1 fusion and content delivery to the infected cells, the tegument protein VP16 binds to the cellular Oct1 and HCF proteins and targets to the viral IE promoter, where it displaces cellular H (1), and activates viral gene expression by recruiting the BTM (2). ICP0 has multiple functions to activate subsequent viral gene expression, including dissociating HDAC complexes (3) and inducing the degradation of PML and Sp100 (4). ICP4 promotes the expression of early and late viral genes by recruiting BTM to targeted promoters (5). BTM: Basal transcriptional machinery; E/L: Early/late; H: Histones; HCF: Host-cell factor; HCMV: Human cytomegalovirus; HDAC: Histone deacetylase; HSV: Herpes simplex virus; IE: Immediate-early; MIEP: Major immediate-early promoter; PML: Promyelocytic leukemia; PML-NB: PML-nuclear body; TF: Transcription factor.

The effects of oe or kd of P, S, or D, or the inhibition of histone deacetylase on viral IE and E gene expression, or the completion of Rep are summarized. Conditions which increase gene expression are denoted in green (↑) and left-aligned; those which have no effect are black (↔) and centered; and those which decrease gene expression are right-aligned and in red (↓). Wild-type viruses and mutants are shown, which lack pp71 (HCMV Δ71), lack IE1 (CR208), lack ICP0 (HSV-1 ΔICP0), or contain nonfunctional VP16 (HSV-1 NF-VP16). D: Daxx; E: Early; HCMV: Human cytomegalovirus; HDI: Histone deacetylase inhibition; HSV: Herpes simplex virus; IE: Immediate-early; kd: knockdown; oe: Overexpression; P: Promyelocytic leukemia protein; Rep: Replication cycle; S: Sp100.