MOLECULAR BIOLOGY OF HERPES SIMPLEX VIRUSES

单纯疱疹病毒（HSV）属于致癌病毒家族， 病毒。 它们会导致中度至重度疾病，特别是在 新生儿，感染或药物诱导的免疫缺陷 包括癌症患者在内的个体，并作为共同- 子宫颈癌的病因 一个关键的财产是他们的 在感觉或自主神经元中保持潜伏的能力， 在自发或诱导激活后引起复发性病变， 病毒复制 该应用程序巩固了四个长期存在的 交叉的项目集中在分子生物学， 这些病毒。 这些项目的主要组成部分如下： （i）HSV基因组由两个共价连接的 两侧为反向重复序列的双链DNA组分。 两个组件共享的终端序列包含 顺式位点，用于两个组分相对于每个组分的反转 另一种是从多聚体头部切除基因组， 尾多联体，用于将DNA包装到衣壳中，以及用于 DNA的环化。 a序列包含 转录起始位点和基因的启动子，所述基因 编码序列在长组分的重复中。 这些 将继续进行研究，以确定病毒的反式作用因子 与a序列特异性结合， 通过其基因的突变和顺式作用的突变来发挥功能， 网站. (ii)技术已经发展并应用于 证明了除了一个基因图谱之外， 小（S）分量的序列关于 病毒在细胞培养中的生长。 目的是继续 分析病毒基因组中的p53基因，以确定 他们的功能，并确定一个新的基本功能， 在其结构域中含有DNA的S组分来源的基因 合成. (iii)HSV基因形成三个主要组α，β， 和γ，其表达以级联方式调节。 α基因是由一种结构成分诱导的， 但是诱导病毒颗粒所需的顺式作用位点 α基因结合两种宿主蛋白质。 计划是继续 描述病毒因子与这些因子的相互作用， 蛋白质，并确定这些蛋白质在 α基因的诱导，以及主要的 调节蛋白，α 4，调节β和γ 基因. (iv)只有一个病毒基因的子集在潜伏期表达， 感染神经元。 目标是通过基因工程 新的基因组，以确定为什么病毒的完整补充， 基因在潜伏期不表达。

Herpes simplex viruses (HSV) belong to a family of oncogenic viruses. They cause moderate to severe disease, particularly in neonates, infection or drug induced immunologically deficient individuals including cancer patients and are associated as co- factors with human cancer of the cervix. A key property is their ability to remain latent in sensory or autonomic neurons and to cause recurrent lesions after spontaneous or induced activation of viral replication. This application consolidates four long standing interdigitated projects centering on the molecular biology of these viruses. The key components of these projects are as follows: (i) The HSV genome consists of two covalently linked double stranded DNA components flanked by inverted repeats. The terminal a sequence shared by both components contains the cis sites for the inversion of the two components relative to each other, for the excision of the genome from multimeric head to tail concatemers, for packaging of the DNA into capsids, and for the circularization of the DNA. The a sequence contains the transcription initiation site and the promoter of a gene whose coding sequence are in the repeats of the long component. These studies will be continued to identify the viral trans-acting factors that specifically bind to the a sequence and to determine their function by mutage- nesis of their genes and of their cis-acting sites. (ii) Technology has been developed and applied to demonstrate that all but one gene mapping in the unique sequences of the small (S) component are dispensable with respect to viral growth in cell culture. The intent is to continue the analyses of the viral genome for dispensable genes, to determine their function, and to determine the function of a new essential gene which contain in its domain the S component origins of DNA synthesis. (iii) HSV genes form three major groups alpha, beta, and gamma whose expression is regulated in a cascade fashion. The alpha genes are induced by a structural component of the virion but that the cis-acting site required for the induction of the alpha genes binds two host proteins. The plan is to continue to characterize the interaction of the viral factor with these proteins and to determine the role of these proteins in the induction of alpha genes, as well as the role of the major regulatory protein, alpha 4, in the regulation of beta and gamma genes. (iv) Only a subset of viral genes in expressed during latent infection of neurons. The objectives are to genetically engineer novel genomes to determine why the full complement of viral genes is not expressed during latency.