Varicella-zoster virus (VZV), a neurotropic alphaherpes virus, is the etiologic agent of two distinct clinical syndromes: chickenpox (varicella) and shingles (zoster). VZV is an enveloped virus with a linear double- stranded genome of approximately 125,000 base pairs (bp). The complete genomic nucleotide sequence of VZV has been determined and predicts approximately 70 unique genes. The expression of VZV genes appear to be temporally regulated and three putative kinetic classes have been defined for VZV genes; namely immediate early, early and late. Evolving evidence suggest that the putative immediate early gene product of ORF62 (IE62) to be the dominant regulatory protein in VZV. In addition, the ORF62 gene has been shown to be transcriptionally active during the latent phase of VZV infection in ganglia, thus suggesting a potential role for this gene in the maintenance of latency. Current efforts focus on the structure-function analysis of IE62 regulatory protein using a variety of genetic approaches. The 75-amino acid activation domain of the IE62 is being probed to identify amino acids of high informational content, both by site-specific mutagenesis and regionally-directed, saturation mutagenesis. Our recent studies have illustrated that the IE62-dependent activation or responsive promoters are mediated by a unique mechanism involving the TATA element of the eukaryotic promoters. However, the magnitude of transcriptional activation appears to be imparted by a region of the protein other than the N-terminal activation domain. Consistent with this observation, we have identified a region that maps to the central portion of the 1310- amino acid polypeptide that physically interact with the two critical basal transcription factors, namely, TBP and TFIIB. These studies, thus have presented us with the challenge of dissecting the mechanism of transcriptional activation by a potent viral transactivation domain lacking any inherent ability to directly interact with either the TBP or TFIIB.
