CELLULAR HOMOLOGS OF HERPESVIRUS GENES

疱疹病毒基因的细胞同源物

• 批准号: 3746683
• 负责人: J I COHEN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3746683
• 关键词: Epstein Barr virus; Herpesviridae; gene expression; guinea pigs; host organism interaction; latent virus infection; molecular cloning; nucleic acid sequence; thymidylate synthase; varicella zoster virus; virus genetics

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.

疱疹病毒引起潜伏感染，持续一生， 宿主和这些病毒已经发展出对抗宿主机制 让病毒继续存在。 使用复杂 我们正在用计算机程序识别疱疹病毒的基因， 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 影响免疫系统，影响感染过程。 这些基因的鉴定可能有助于定义抗病毒药物的新靶点 治疗或调节免疫系统的新见解。 水痘-带状疱疹病毒（VZV）ORF 13编码病毒胸苷酸 合成酶 这种酶催化脱氧尿苷酸的甲基化， 胸苷酸。 我们已经构建了一个VZV突变体，它不能表达 通过在基因中插入终止密码子来改造病毒胸苷酸合成酶。 我们 计划用VZV突变体感染豚鼠，以确定 病毒胸苷酸合成酶对于感染 病毒或其传播到中枢神经系统的能力， 保持潜伏感染。 EB病毒（EBV）编码一种蛋白质，含有七个推定的 跨膜结构域和共享同源性的G蛋白偶联 受体超家族 我们已经克隆了这个EB病毒基因，表达了一种蛋白质， 目前正在检测这种蛋白质的生物活性 已知哺乳动物蛋白质的其它疱疹病毒同源物已被发现。 鉴定 有前途的候选人将在适当的系统中进行研究 与M.免疫公司的斯普里格斯