ROLE OF VARICELLA ZOSTER VIRUS GLYCOPROTEIN B DURING VIR

疱疹病毒是几种人类疾病的罪魁祸首，包括水痘、带状疱疹、口腔和生殖器疱疹，以及免疫系统薄弱者的危及生命的感染。水痘-带状疱疹病毒(VZV)和所有疱疹病毒一样，有一层对传染性至关重要的外膜。当病毒衣壳从受感染细胞的细胞核通过内核膜时，它就获得了最初的膜。在那之后，VZV获得其最终感染能力包膜的确切机制，以及它从受感染细胞排出时所遵循的路线尚不清楚。然而，众所周知，疱疹病毒的出口需要几种病毒编码的糖蛋白的高尔基依赖的成熟。这强调了病毒糖蛋白运输对疱疹病毒组装和输出的关键重要性。糖蛋白B(Gb)是一种存在于所有疱疹病毒中的蛋白质，被认为是病毒从受感染细胞正常排出的关键。与大多数疱疹病毒膜蛋白不同，gB具有一个很长的细胞质结构域，该结构域与其自身的细胞内转运和病毒出口有关。然而，胞浆结构域GB中的特定细胞内靶向序列尚未在任何疱疹病毒中被鉴定，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VZV gB胞浆区域内其细胞内转运所需的特定信号序列；(Ii)确定gB胞内转运的中断是否影响病毒的组装和输出；以及(Iii)确定改变gB转运的突变如何影响VZV在培养细胞和人类组织中的生长。这项研究可能会确定关键的病毒代谢途径，并最终可能导致新的抗病毒疗法的开发。

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.