GENETIC AND BIOCHEMICAL STUDIES OF THE HSV IE-O GENE

这八种人类疱疹病毒都具有在特定靶组织中引发原发性感染并随后以潜伏形式自我隔离的能力。 根据初次感染的部位和潜伏期发现的部位，将构成该家族的病毒分为三类。 该家族的两个成员爱泼斯坦巴尔肉瘤和卡波西肉瘤与人类肿瘤的产生有关。 这些含有大双链DNA的病毒的基因表达调控是由基因表达的时序级联引起的。 该基金主要用于研究单纯疱疹病毒（HSV）感染细胞的基因表达调控，HSV是α疱疹病毒科病毒的原型。即早（IE）基因的表达负责HSV基因表达的协调调节。该实验室的工作重点是表征IE基因产物的活性。 特别地，我们研究了IE-O、IE-4和IE-27基因座的基因产物。 这些分析揭示了ICPO和ICP 27的新功能，并证明了ICP 4和27相互作用。 在本申请中将研究的ICP 27的新特征是其RNA依赖性穿梭活性。 我们将继续我们的研究，这些基因产品使用遗传和生物化学方法来检查突变的影响，这些蛋白质的编码序列。 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.