GENETIC AND BIOCHEMICAL STUDIES OF THE HSV IE-O GENE

这八种人类疱疹病毒都有能力在特定的目标组织中发起初级感染，然后以潜伏的形式自我隔离。构成这个家族的病毒根据其主要感染发生的地点和在潜伏期发现的地点被分成三类。这个家族的两个成员Epstein Barr和Kaposi肉瘤与人类肿瘤的发生有关。这些含有大的双链DNA的病毒的基因表达的调节是由基因表达的时间顺序级联引起的。这笔赠款涉及对感染单纯疱疹病毒(HSV)的细胞中基因表达的调控。单纯疱疹病毒是甲型疱疹病毒科的原型。即刻早期(IE)基因的表达负责协调HSV基因的表达。本实验室致力于研究IE基因产物的活性。特别是对IE-O、IE-4和IE-27基因座的基因产物进行了研究。这些分析揭示了ICPO和ICP27的新功能，并证明了ICP4和ICP27之间存在相互作用。将在这一应用中研究的ICP27的新特征是其依赖RNA的穿梭活性。我们将继续使用遗传和生化方法对这些基因产物进行研究，以检查突变对编码这些蛋白质的序列的影响。这些研究将有助于理解这些病毒如何与宿主相互作用，以及病毒特定的蛋白质-蛋白质和宿主-病毒相互作用的后果是什么。

The eight human herpes viruses share the ability to initiate a primary infection in a specific target tissue and to subsequently sequester themselves in a latent form. The viruses that compose this family are grouped into three classes on the basis of the site of where their primary infection occurs and where they are found during latency. Two members of this family Epstein Barr and Kaposi's Sarcoma have been implicated in the generation of tumors in humans. Regulation of gene expression from these large double-stranded DNA containing viruses results from a temporally ordered cascade of gene expression. This grant is concerned with regulation of gene expression in cells infected with herpes simplex virus (HSV), the prototype for the alphaherpesviridae. It is the expression of immediate early (IE) genes that is responsible for coordinate regulation of HSV gene expression. This laboratory has focused its efforts on characterizing the activities of IE gene products. In particular we have studied the gene products of the IE-O, IE-4 and IE-27 loci. These analyses have revealed novel functions for both ICPO and ICP27, and demonstrated that ICPs 4 and 27 interact. The novel feature of ICP27 that will be studied in this application is its RNA- dependent shuttling activity. We will continue our studies of these gene products using genetic and biochemical approaches to examine the effects of mutations to the sequences encoding these proteins. These studies will add to the understanding of how these viruses interact with their host and what the consequences of virus specified protein-protein and host-virus interactions are.