FIGURE 1.

Domain structure and mechanism of VP16 to promote IE gene transcription. (A) Domain structure of HSV-1 VP16. The DBD can bind to the promoter of IE genes stably through interaction with HCF-1 and Oct-1, and the TAD of HSV VP16 can be divided into two regions, H1 and H2, which can bind to different transcriptional activators and also synergistically interact with some important transcriptional factors (Ikeda et al., 2002; Hirai et al., 2010). (B) The schematic of various VP16 homologs with their functional domains. The DBD is conserved in VP16 homologs, but the TADs of VP16 homologs are not conserved in position, sequence, or amino acid properties. The VP16 TAD of HSV and EHV is located at the C-terminus, but in BHV and VZV, the VP16 TAD is located at the N-terminus (Cohen and Seidel, 1994; Wysocka and Herr, 2003; Tyack et al., 2006). (C) Mechanism of VP16 to promote IE gene transcription. The DNA-binding ability of VP16 itself is weak, and the binding is unstable; VP16 mainly combines with HCF-1 and Oct-1 to form a complex through the unstructured region in its DBD, so as to bind stably to the specific site of the target gene promoter and then recruit transcriptional factors through the TAD to promote the transcription of the target gene. The formation of the complex by VP16, HCF-1, and Oct-1 is the most effective combination by VP16 dominated to activate viral gene cascade expression. The VP16-induced complex represents a regulatory switch for two modes of viral infection: lytic infection and latent infection. When it is “on,” it promotes the transcription of IE genes and thus lytic infection, and when it is “off,” limiting IE gene transcription, viruses can maintain established latent infections (Wysocka and Herr, 2003; Hirai et al., 2010; Milbradt et al., 2011).