GENETIC AND BIOCHEMICAL STUDIES OF THE HSV IE-O GENE

八种人类疱疹病毒都具有在特定目标组织中引发原发性感染并随后以潜伏形式将自身隔离的能力。构成这一科的病毒根据其初次感染发生的地点和在潜伏期发现的地点分为三类。这个家族的两个成员爱泼斯坦·巴尔和卡波西肉瘤与人类肿瘤的产生有关。这些含有病毒的大双链DNA的基因表达调控源于基因表达的时序级联。这项拨款是关于感染单纯疱疹病毒（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。直接早期（IE）基因的表达负责协调调节HSV基因的表达。该实验室的工作重点是描述IE基因产物的活性。我们特别研究了IE-O、IE-4和IE-27位点的基因产物。这些分析揭示了ICPO和ICP27的新功能，并证明icp4和ICP27相互作用。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来研究这些基因产物，以检查突变对编码这些蛋白质的序列的影响。这些研究将有助于了解这些病毒如何与宿主相互作用，以及病毒特异性蛋白质-蛋白质和宿主-病毒相互作用的后果。

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.