CELLULAR HOMOLOGS OF HERPESVIRUS GENES

疱疹病毒会导致潜伏感染，这种感染会持续一生 宿主和这些病毒已经形成了中和宿主的机制 进行防御，以使病毒持续存在。使用复杂的 计算机程序我们正在识别具有细胞性的疱疹病毒基因 同系物。这些基因在不同的系统中表达 确定基因如何与宿主细胞蛋白相互作用，包括 免疫系统的那些，影响感染的过程。 识别这些基因可能有助于确定抗病毒的新靶点 治疗或对调节免疫系统的新见解。 水痘-带状疱疹病毒(VZV)ORF13编码一种病毒胸苷 合成酶。这种酶催化脱氧尿酸甲基化以 胸腺嘧啶。我们已经构建了一个VZV突变体，它不能表达 病毒胸苷合成酶通过在基因中插入终止密码子。我们 计划给豚鼠接种VZV突变体，以确定 病毒胸苷合成酶对于感染人胸腺病毒很重要。 病毒或其传播到中枢神经系统的能力以及 保持潜伏感染。 爱泼斯坦-巴尔病毒(Epstein-Barr Virus，EBV)编码一种蛋白质，该蛋白质含有7种推定的 跨膜结构域与G蛋白偶联的同源性 受体超家族。我们已经克隆了这个EBV基因，表达了一种蛋白质， 目前正在测试这种蛋白质的生物活性。 已知的哺乳动物蛋白的其他疱疹病毒同源物已经被 已确认身份。有希望的候选人将在适当的系统中进行研究 与M.Spriggs在免疫系统的合作。

Herpesviruses cause latent infections that persist for the lifetime of the host and these viruses have developed mechanisms to counteract host defenses so as to allow the virus to persist. Using sophisticated computer programs we are identifying herpesvirus genes that have cellular homologs. These genes are being expressed in various systems to determine how the genes may interact with host cell proteins, including those of the immune system, to influence the course of infection. Identification of these genes may help define new targets for antiviral therapy or new insights into modulating the immune system. Varicella-zoster virus (VZV) ORF13 encodes a viral thymidylate synthetase. This enzyme catalyzes the methylation of deoxyuridylate to thymidylate. We have constructed a VZV mutant that cannot express the viral thymidylate synthetase by inserting stop codons into the gene. We plan to inoculate guinea pigs with the VZV mutant to determine whether the viral thymidylate synthetase is important for infection with the virus or for its ability to spread to the central nervous system and maintain latent infection. Epstein-Barr virus (EBV) encodes a protein that contains seven putative transmembrane domains and shares homology to the G protein-coupled receptor superfamily. We have cloned this EBV gene, expressed a protein, and are currently assaying the protein for biological activity. Additional herpesvirus homologs of known mammalian proteins have been identified. Promising candidates will be studied in appropriate systems in collaboration with M. Spriggs at Immunex.