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α疱疹病毒，是两种疾病的传染源，在初次感染期间引起水痘（水痘），在潜伏期重新激活后引起带状疱疹（带状疱疹）。VZV疫苗现在广泛用于儿童，也可用于老年人以预防带状疱疹。在这种情况下，我们必须能够了解这种重要的人类病毒的复制和毒力机制。在过去的资助期间，我们已经确定了从病毒糖蛋白启动子表达所需的病毒和细胞因子，并在这样做的过程中，已经制定了一个模型的反式激活机制的病毒IE62主要反式激活因子。我们还评估了其他两个重要的病毒蛋白（ORF 29和ORF 63蛋白）在VZV转录调控中的作用。在这个建议中，我们将完善我们的模型IE62激活的VZV gI启动子，并检查这种蛋白质与无处不在的细胞转录因子的相互作用。我们将扩大我们的工作VZV转录的问题，关于潜在的基因表达使用一种新的VZV裂解双向启动子，其功能单向潜伏。最后，我们将研究的性质和功能的相互作用，确定在最后一个资助期间，VZV IE62和ORF 63蛋白之间，并确定后者的蛋白质在VZV基因调控的功能。

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.