STRUCTURAL AND MECHANISTIC STUDIES OF HERPESVIRUS ENTRY INTO CELLS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 疱疹病毒是一种人类病原体，可终身感染宿主，在免疫受损的人中导致唇疱疹、生殖器疱疹、失明、脑炎、癌症和危及生命的疾病。我们研究的目标是从原子水平详细了解疱疹病毒是如何进入宿主细胞的。这些信息在设计抗疱疹病毒疗法以对抗病毒感染和细胞传播方面将是无价的。疱疹病毒进入细胞的机制非常复杂。尽管其他被包膜的病毒只使用一种蛋白质来影响细胞进入，但所有疱疹病毒至少需要三种蛋白质：gB、Gh和gl。这三种蛋白质被认为完成了病毒和细胞膜的融合，这是病毒进入的关键一步，但它们的确切功能尚不清楚。我们的目标是确定单纯疱疹病毒(HSV)的gB和Gh/g1蛋白如何共同完成膜融合，以及来自受体结合蛋白Gd的信号如何触发膜融合机制。揭示这些蛋白在HSV感染中的作用方式也将揭示它们在其他疱疹病毒中的功能，因为膜融合机制，即Gb、Gh和gl是高度保守的。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Herpesviruses are human pathogens that infect their hosts for life, causing cold sores, genital herpes, blindness, encephalitis, cancers, and life-threatening conditions in immuno-compromised individuals. The goal of our research is to understand in atomic-level detail how herpesviruses enter host cells. Such information will be invaluable in designing anti-herpesvirus therapeutics to combat both viral infections and cell-cell spread. The herpesvirus cell-entry mechanism is very complex. Whereas other enveloped viruses use a single protein to effect cell entry, all herpesviruses require at least three proteins: gB, gH, and gL. These three proteins are thought to accomplish the fusion of viral and cell membranes  a pivotal step in viral entry  but their exact functions are obscure. We aim to determine how gB and gH/gL proteins of Herpes Simplex Virus (HSV) work together to accomplish membrane fusion and how the signal from the receptor-binding protein, gD, triggers the membrane-fusion machinery. Uncovering how these proteins work in HSV infection will also reveal their functions in other herpesviruses because the membrane-fusion machinery, i.e., gB, gH, and gL, is highly conserved.