ROLE OF VARICELLA ZOSTER VIRUS GLYCOPROTEIN B DURING VIR

水痘带状疱疹病毒糖蛋白 B 在 VIR 期间的作用

• 批准号: 6349892
• 负责人: Thomas C Heineman
• 金额: $ 26.87万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-15 至 2004-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6349892
• 关键词: SCID mouse; binding proteins; biological signal transduction; chickenpox; electron microscopy; endocytosis; gene expression; glycoproteins; human tissue; immunofluorescence technique; intracellular transport; plasmids; posttranslational modifications; protein localization; recombinant virus; shingles; tissue /cell culture; transfection; varicella zoster virus; virus assembly; virus envelope; virus infection mechanism; virus protein; virus replication

Herpesviruses are responsible for several human diseases including chickenpox, shingles, oral and genital herpes, and life-threatening infections in persons with weakened immune systems. Varicella-zoster virus (VZV), like all herpesviruses, has an outer membrane that is essential for infectivity. It acquires its initial membrane upon the passage of viral capsids from the nucleus of infected cells through the inner nuclear membrane. After that, the precise mechanism by which VZV acquires its final infection-competent envelope, and the route it follows during egress from infected cells is unclear. It is known, however, that herpesvirus egress requires the golgi- dependent maturation of several virus-encoded glycoproteins. This emphasizes the critical importance of viral glycoprotein transport for herpesvirus assembly and egress. Glycoprotein B (gB), a protein represented in all herpesviruses, is thought to be vital for the normal egress of virus from infected cells. Unlike most herpesvirus membrane proteins, gB possesses a long cytoplasmic domain that has been implicated in its own intracellular transport as well as in viral egress. However, specific intracellular targeting sequences within the cytoplasmic domain gB have not been identified for any of the herpesviruses, nor is it known what impact mutations in these sequences may have on viral assembly and growth. We propose to (i) identify the specific signal sequences within the cytoplasmic domain VZV gB that are required for its intracellular transport; (ii) determine whether disruption of gB intracellular transport affects virus assembly and egress; and (iii) determine how mutations that alter the transport of gB affect VZV growth in cultured cells and in human tissue. This research may identify critical viral metabolic pathways and may ultimately lead to the development of new antiviral therapies.

疱疹病毒是导致几种人类疾病的原因，包括水痘、带状疱疹、口腔和生殖器疱疹，以及免疫系统减弱的人的危及生命的感染。 水痘带状疱疹病毒（VZV），像所有疱疹病毒，有一个外膜，是必不可少的感染性。 当病毒衣壳从受感染细胞的细胞核穿过内核膜时，它获得其初始膜。 在此之后，VZV获得其最终感染能力包膜的确切机制，以及它从感染细胞中流出的路线尚不清楚。 然而，已知疱疹病毒的排出需要几种病毒编码的糖蛋白的高尔基体依赖性成熟。这强调了病毒糖蛋白转运对于疱疹病毒组装和外出的至关重要性。 糖蛋白B（gB）是一种存在于所有疱疹病毒中的蛋白质，被认为对病毒从感染细胞中正常排出至关重要。与大多数疱疹病毒膜蛋白不同，gB具有一个长的胞质结构域，该结构域与其自身的细胞内转运以及病毒外出有关。 然而，胞质结构域gB内的特异性细胞内靶向序列尚未被确定为任何疱疹病毒，也不知道这些序列中的突变可能对病毒组装和生长产生什么影响。 我们建议（i）确定胞质结构域VZV gB内的特定信号序列，其胞内运输所需的;（ii）确定是否破坏gB胞内运输影响病毒组装和出口;（iii）确定如何改变运输的突变gB影响VZV在培养细胞和人体组织中的生长。 这项研究可能会确定关键的病毒代谢途径，并可能最终导致新的抗病毒疗法的发展。