Varicella zoster virus (VZV) is a ubiquitous human alphaherpesvirus, which is the infectious agent of two diseases, causing varicella (chickenpox) during primary infection and zoster (shingles) after reactivation from latency. A VZV vaccine is now in widespread use in children and may also be used in older adults in order to prevent zoster. In these contexts, it is essential for us to be able to understand the mechanisms of replication and virulence of this important human virus. During the past funding period we have identified the viral and cellular factors required for expression from a viral glycoprotein promoter and in doing so, have formulated a model for the mechanism of transactivation by the viral IE62 major transactivator. We have also assessed the roles of two other essential viral proteins (ORF 29 and ORF 63 proteins) in the regulation of VZV transcription. In this proposal we will refine our model of IE62 activation of the VZV gI promoter and examine the interaction of this protein with ubiquitous cellular transcription factors. We will expand our work on VZV transcription into questions regarding latent gene expression using a novel VZV lytic bidirectional promoter which functions unidirectionally in latency. Finally, we will examine the nature and the function of the interaction, identified during the last funding period, between the VZV IE62 and ORF 63 proteins and determine the function of the latter protein in VZV gene regulation.
