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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要神经侵袭性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，并且是重要原因发病率和死亡率。干扰病毒体结构重排的新策略感染性所需的病毒可能对治疗感染有价值，但病毒体的关键方面架构及其亚稳定性仍然没有明确的定义。在此应用程序中，我们概述了一个策略识别细胞外病毒颗粒内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 之间存在条件相互作用衣壳有助于感染的关键步骤，包括病毒分解和调节 pUL36 去泛素酶活性：α-疱疹病毒建立终生生命所需的过程神经系统感染。