Interactions between varicella-zoster virus IE62 and cellular transcription factor USF in the coordinate activation of genes 28 and 29.

Varicella-zoster virus (VZV) gene 28 encodes the viral DNA polymerase, while 29 encodes the major DNA-binding protein. Because of the central importance of these proteins to productive replication of VZV and because, of these, only gene 29 seems to be expressed in latency, we sought to understand how their expression is controlled. We recently reported that the divergent gene 28 and gene 29 transcripts are coordinately upregulated by IE62. Deletions in the 221-bp promoter domain shared by genes 28 and 29 comparably diminish the expression of both genes. By a variety of transient expression, competition gel shift, and super-shift assays, we now show that cellular transcription factor USF binds to a palindromic recognition sequence lying equidistant from transcription start sites for both genes 28 and 29. In the presence of IE62, USF fully activates transcription of genes 28 and 29. Site-specific mutation of three bases in the USF core binding hexamer abrogates activation of the gene 28 and 29 promoters by IE62. USF is important for expression of genes 28 and 29 in productive VZV infection.