UL34 and herpes simplex virus envelopment

UL34 和单纯疱疹病毒包膜

基本信息

批准号：
7577503
负责人：
RICHARD J ROLLER
金额：
$ 24.59万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-02-01 至 2011-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7577503
关键词：
Affinity Chromatography Binding Biochemical Capsid Capsid Proteins Cell Nucleus Cell physiology Cells Charge Complex Funding Generations Genetic Genome Goals Hand Health Herpesviridae Herpesvirus 1 Human Hybrids In Vitro Infection Laboratories Libraries Mediating Membrane Modeling Mutagenesis Nuclear Envelope Nuclear Inner Membrane Nuclear Lamina Nucleocapsid Play Process Production Proteins Recruitment Activity Research Role Simplexvirus Site Spectrometry Structure System Testing Viral Viral Proteins Virion Virus Work Yeasts base mutant prevent protein function reconstitution research study

Affinity Chromatography Binding Biochemical Capsid Capsid Proteins Cell Nucleus Cell physiology Cells Charge Complex Funding Generations Genetic Genome Goals Hand Health Herpesviridae Herpesvirus 1 Human Hybrids In Vitro Infection Laboratories Libraries Mediating Membrane Modeling Mutagenesis Nuclear Envelope Nuclear Inner Membrane Nuclear Lamina Nucleocapsid Play Process Production Proteins Recruitment Activity Research Role Simplexvirus Site Spectrometry Structure System Testing Viral Viral Proteins Virion Virus Work Yeasts base mutant prevent protein function reconstitution research study

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项目摘要

Herpesviruses replicate and packagetheir genomes in the cell nucleus. In order to begin its processof escape from the cell, the virus must pass through the nuclear membrane by first budding into the inner nuclear membrane in a process called primary envelopment. The mechanism of herpesvirus envelopment is significant to human health from two points of view. First, this process represents an attractive target for therapy in that it is dissimilar in many waysto any normal cellular process, essential to the virus, and common to all herpesviruses. Second, the envelopment machinery alters the organization of the nucler anvelope and provides a usefultool for studying that organization. The research proposed here builds on our studies of herpes simplex virus UL34, an essential component of the envelopment apparatus. Results from our initialperiod of funding suggest that this protein plays critical roles inat least three aspects of envelopment including (i) Recruitment of viral proteins to the nuclear envelope, (ii)dispersal of nuclear envelope components that prevent access of the capsid to the nuclear membrane, and (iii)wrapping of the nucleocapsid in the nuclear membrane. The specific goals of the proposed research are threefold 1. We will define essential functions of the UL34 protein by characterizing a set of seven non-functional mutant UL34 proteins already in hand, and others that we will generate by mutagenesis of conserved residues, for their~ability1o perform various functions required for envelopment. 2. We will characterize critical interactions between the UL34 protein and other viral proteins involved in envelopment. This will include experiments to test the hypothesis that UL34 mediates membrane wrapping of the capsid, and a screen for interactions of UL34 with other viral proteins that may participate in envelopment. 3. We will fully characterize changes in the host cell nuclear lamina associated with infection and determine the mechanism by which UL34 and other viral proteins accomplish those changes.

疱疹病毒在细胞核中复制和包装基因组。为了开始其过程逃离细胞，病毒必须首先萌芽进入内部核膜在称为主要包膜的过程中。疱疹病毒信封的机制是从两个角度来看，对人类健康意义重大。首先，此过程代表了一个有吸引力的目标治疗是因为它在许多正常细胞过程中都不相同，对病毒至关重要，并且所有疱疹病毒共有。第二，包络机器改变了核的组织 Anvelope并为研究该组织提供了有用的工具。这里提出的研究基于我们对单纯疱疹病毒UL34的研究，这是一个重要的组成部分信封设备。我们初始资金的结果表明该蛋白质发挥作用关键作用至少在包膜的三个方面，包括（i）募集病毒蛋白到核信封，（ii）散布核包络组件，以防止capsid进入核能膜和（iii）核膜中的核素包裹。拟议研究的具体目标是三倍 1。我们将通过表征一组七个非功能性来定义UL34蛋白的基本功能突变的UL34蛋白已经在手里，其他我们将通过保守的诱变产生的其他蛋白残留物，因为它们的能力1O执行包裹所需的各种功能。 2。我们将表征UL34蛋白与其他参与的病毒蛋白之间的关键相互作用信封。这将包括测试UL34介导膜包裹的假设的实验 capsid的内容，以及UL34与其他可能参与的病毒蛋白相互作用的屏幕信封。 3。我们将充分表征与感染相关的宿主细胞核层的变化并确定 UL34和其他病毒蛋白实现这些变化的机制。