ANATOMY OF THE VARICELLA-ZOSTER VIRUS OPEN-READING FRAME-4 PROMOTER

The regulation of varicella-zoster virus (VZV) gene expression is larg ely controlled at the transcriptional level by a few key viral protein s cooperating with one another and with cellular transcription factors . However, the mechanisms involved are largely unclear. To identify th e sequences important for the transcriptional regulation of open-readi ng frame (ORF) 4, itself encoding a transcriptional regulator, a mutat ion analysis of the promoter was done. These studies identified an ele ment between -69 and -59 (relative to the transcriptional start site), which was critical to the activity of the promoter upon stimulation b y the VZV transactivator IE62 and by VZV infection. DNA-protein intera ction studies revealed that VZV induced the binding of a specific prot ein complex to this element, which contained the ubiquitous transcript ion factor USF. ORF 4 is the second VZV gene (in addition to VZV ORF 2 9) in which USF binding plays a critical role in gene expression.