Dynamic interactions within alpha-herpesvirus virions and their impact on infection

项目摘要 神经侵入性α疱疹病毒，例如单纯疱疹病毒（HSV）和伪狂犬病病毒 (PRV)在人类和其他动物中引起广泛的疾病， 发病率和死亡率。干扰病毒体结构重排的新策略 所需的感染性可能被证明是有价值的治疗感染，但关键方面的病毒粒子 体系结构及其亚稳定性仍然没有得到很好的定义。在这个应用程序中，我们概述了一个策略 以确定细胞外病毒颗粒内的动态蛋白质相互作用。拟议研究 将检验这样的假设，即基本病毒蛋白pUL 36 和衣壳有助于感染的关键步骤，包括病毒分解和调节 pUL 36去泛素化酶活性：α-疱疹病毒建立终身免疫所需的过程 神经系统感染。

PROJECT SUMMARY Neuroinvasive alpha-herpesviruses such as herpes simplex virus (HSV) and pseudorabies virus (PRV) cause a broad range of diseases in humans and other animals and are significant causes of morbidity and mortality. Novel strategies to interfere with the virion structural rearrangements required for infectivity could prove valuable to treat infections, yet critical aspects of the virion architecture and its metastability remain poorly defined. In this application, we outline a strategy to identify dynamic protein interactions within extracellular viral particles. The proposed research will test the hypothesis that conditional interactions between the essential viral protein pUL36 and capsids contribute to critical steps in infection including viral disassembly and regulation of pUL36 deubiquitinase activity: processes required for alpha-herpesviruses to establish life-long infection of the nervous system.