UL34 and herpes simplex virus envelopment

UL34 和单纯疱疹病毒包膜

基本信息

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
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

项目摘要

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。为了开始其从细胞逃脱的过程，该病毒必须在一个称为主要包膜的过程中首先萌芽进入内部核膜。从两种角度来看，疱疹病毒包络的机制对人类健康至关重要。首先，此过程代表了一个有吸引力的治疗靶标，因为它在许多方面与任何正常的细胞过程不同，这对病毒至关重要，并且对所有疱疹病毒来说都是常见的。其次，信封机械改变了核信封的组织，并为研究该组织提供了有用的工具。这里提出的研究基于我们对疱疹病毒UL34的研究，这是信封仪器的重要组成部分。我们最初的资金阶段的结果表明，该蛋白在包裹的至少三个方面起着至关重要的作用，包括（i）病毒蛋白募集到核包膜上，（ii）散布核包膜成分，以防止cap孔进入核膜上，以及（iii）（iii）（iii）（iii）在核膜膜中包裹。拟议研究的具体目标是三倍 1。我们将通过表征已经掌握的七个非功能突变体UL34蛋白的表征来定义UL34蛋白的基本功能，而其他我们将通过诱变保守残基产生的其他功能，因为它们具有执行包封所需的各种功能的能力。 2。我们将表征UL34蛋白与包裹中其他病毒蛋白之间的关键相互作用。这将包括测试UL34介导膜包裹的假设的实验，以及UL34与其他可能参与包膜的病毒蛋白相互作用的屏幕。 3。我们将充分表征与感染相关的宿主细胞核椎板的变化，并确定UL34和其他病毒蛋白可以完成这些变化的机制。