Structure/Function of Varicella Zoster Virus DNA

描述（由申请人提供）：水痘带状疱疹病毒（VZV）是一种普遍存在的人类甲疱疹病毒，它是两种疾病的传染因子，在初次感染时引起水痘（水痘），在潜伏期重新激活后引起带状疱疹（带状疱疹）。VZV疫苗目前在儿童中广泛使用，也可能在老年人中使用，以预防带状疱疹。在这种情况下，我们有必要了解这种重要的人类病毒的复制机制和毒力。在过去的资助期间，我们已经确定了病毒糖蛋白启动子表达所需的病毒和细胞因子，并在此过程中制定了病毒IE62主要反激活因子反激活机制的模型。我们还评估了另外两种必需的病毒蛋白（ORF 29和ORF 63蛋白）在VZV转录调控中的作用。在这个提议中，我们将完善我们的IE62激活VZV gI启动子的模型，并检查该蛋白与普遍存在的细胞转录因子的相互作用。我们将利用一种新型的VZV裂解双向启动子将VZV转录扩展到潜在基因表达的问题，该启动子在潜伏期中单向起作用。最后，我们将研究在上一个资助期内发现的VZV IE62和ORF 63蛋白之间相互作用的性质和功能，并确定后者蛋白在VZV基因调控中的功能。

DESCRIPTION (provided by applicant): 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.