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

α-疱疹病毒病毒粒子内的动态相互作用及其对感染的影响

• 批准号: 10042917
• 负责人: Gregory Allan Smith
• 金额: $ 23.7万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10042917
• 关键词: Acyclovir; Alphaherpesvirinae; Animals; Antiviral Agents; Architecture; Attenuated; Binding; Capsid; Cell Nucleus; Cells; Clinical; Development; Disease; Encephalitis; Epithelial; Epithelium; Event; Foundations; Genome; Goals; Herpes zoster disease; Herpesviridae; Herpesvirus 1; Human; Human Herpesvirus 2; Infection; Keratitis; Life; Methods; Modeling; Molecular; Morbidity - disease rate; Mutagenesis; Mutate; Neurons; Pathogenesis; Process; Property; Proteins; Reagent; Regulation; Research; Resources; Role; Simplexvirus; Structure; Testing; United States; Viral; Viral Genome; Viral Proteins; Virion; Virus; Virus Assembly; Work; design; extracellular; fluorescence imaging; gain of function; human pathogen; imaging modality; mad itch virus; member; mortality; neonatal infection; nervous system infection; neurovirulence; novel strategies; novel vaccines; particle; tool; transmission process; vaccine candidate

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.

项目摘要 神经脱落的α-疱疹病毒，例如单纯疱疹病毒（HSV）和假病毒病毒 （PRV）引起人类和其他动物的广泛疾病，是重大原因 发病率和死亡率。干扰病毒体结构重排的新型策略 感染性所需 建筑及其可竞争能力的定义仍然很差。在此应用程序中，我们概述了策略 鉴定细胞外病毒颗粒中的动态蛋白质相互作用。拟议的研究 将检验以下假设：必需病毒蛋白PUL36之间的条件相互作用 和衣壳助长感染的关键步骤，包括病毒拆卸和调节 PUL36去泛素酶活性：α-疱疹病毒所需的过程才能建立终身 神经系统的感染。