VP16

VP16 is a major tegument protein of herpes simplex virus type 1 (HSV-1) that functions as a transcriptional activator of the virus’s immediate-early genes. It is sometimes called α-TIF (alpha transcriptional initiator factor) due to its key role at the start of viral gene expression after infection.

In HSV-1 infection, VP16 is delivered to the nucleus in the virion and binds to promoter regions through an indirect DNA-recognition mechanism. The protein interacts with the host transcription factor Oct-1 and the coactivator HCF-1 to form a transcriptional activation complex that binds to the TAATGARAT motif present in many immediate-early promoters. This complex recruits the cellular transcription machinery, including components of TFIID and the Mediator complex, leading to rapid transcription of immediate-early genes such as ICP0, ICP4, ICP27, and ICP22. Action by VP16 sets off a cascade that enables subsequent early and late viral gene expression and viral replication.

Structurally, VP16 has an N-terminal region that participates in DNA engagement and a C-terminal activation domain that recruits coactivators. Its activity can be modulated by phosphorylation and interactions with other host factors. VP16 serves as a model transcriptional activator in molecular biology and, in research contexts, its activation domain is frequently used in fusion constructs to robustly drive gene expression. Related herpesviruses encode VP16 homologs with similar roles in initiating transcription.