Varicella-zoster virus DNA polymerase and major DNA-binding protein genes have overlapping divergent promoters.

A detailed analysis of the transcriptionally divergent promoters of varicella-zoster virus (VZV) open reading frames (ORFs) 28 and 29, encoding the DNA polymerase and major DNA-binding proteins, respectively, was performed. We found that the 221-bp ORF 28-29 intergenic domain contains overlapping divergent promoters; these promoters have TATA boxes and cap sites arranged closely back-to-back, have highly concordant patterns of responsiveness to transactivation by VZV ORFs 4 and/or 62, and could not be separated without abolishing the effects that VZV trans activators imparted to them. Mutation of the ORF 28 TATA box rendered this promoter unresponsive to ORF 62 and the combination of ORFs 4 and 62 without altering ORF 29 promoter activity. Mutations of all potential ORF 29 TATA boxes collectively failed to abolish this promoter's responsiveness to either ORF 4 or ORF 62, suggesting a mechanism of gene regulation for ORF 29 that differs from that of ORF 28. These findings are concordant with the observation that both genes are expressed in productive infection, but only ORF 29 expression has been identified in latency.