UL34 and herpes simplex virus envelopment

UL34 和单纯疱疹病毒包膜

• 批准号: 7033381
• 负责人: RICHARD J ROLLER
• 金额: $ 25.81万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 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/7033381
• 关键词: Alphaherpesvirinae; affinity chromatography; capsid; cell line; herpes simplex virus 1; herpes simplex virus 2; host organism interaction; liquid chromatography mass spectrometry; nuclear membrane; nucleocapsid; protein protein interaction; protein structure function; recombinant proteins; site directed mutagenesis; virus envelope; virus genetics; virus infection mechanism; virus protein; virus replication; yeast two hybrid system

DESCRIPTION (provided by applicant): Herpesviruses replicate and package their genomes in the cell nucleus. In order to begin its process of 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 ways to any normal cellular process, essential to the virus, and common to all herpesviruses. Second, the envelopment machinery alters the organization of the nuclear envelope and provides a useful tool 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 initial period of funding suggest that this protein plays critical roles in at 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 ability to 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.

描述（由申请人提供）：疱疹病毒在细胞核中复制并包装其基因组。为了开始从细胞逃逸的过程，病毒必须穿过核膜，首先在称为初级包膜的过程中出芽进入内核膜。从两个角度来看，疱疹病毒包膜机制对人类健康具有重要意义。首先，这个过程代表了一个有吸引力的治疗目标，因为它在许多方面与任何正常细胞过程不同，对病毒至关重要，并且是所有疱疹病毒所共有的。其次，包膜机制改变了核膜的组织，并为研究该组织提供了有用的工具。 这里提出的研究建立在我们对单纯疱疹病毒 UL34 的研究基础上，该病毒是包膜装置的重要组成部分。我们最初资助阶段的结果表明，这种蛋白质至少在包膜的三个方面发挥着关键作用，包括（i）将病毒蛋白招募到核膜，（ii）阻止衣壳进入核膜的核膜成分的分散，以及（iii）将核衣壳包裹在核膜中。 拟议研究的具体目标有三个 1. 我们将通过表征一组已经掌握的七个非功能性突变 UL34 蛋白以及我们将通过保守残基诱变产生的其他蛋白来定义 UL34 蛋白的基本功能，因为它们能够执行包封所需的各种功能。 2. 我们将描述 UL34 蛋白和参与包膜的其他病毒蛋白之间的关键相互作用。这将包括测试 UL34 介导衣壳膜包裹这一假设的实验，以及筛选 UL34 与可能参与包裹的其他病毒蛋白相互作用的实验。 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。