UL34 and herpes simplex virus envelopment

疱疹病毒在细胞核中复制并打包它们的基因组。为了开始它的进程 病毒从细胞中逃逸时，必须首先通过核膜发芽进入核内 核膜在一个称为初级包膜的过程中。疱疹病毒包膜的机制是 从两个角度来看，这对人类健康具有重要意义。首先，这一过程是一个有吸引力的目标 治疗方法在许多方面不同于任何正常的细胞过程，对病毒至关重要，而且 所有疱疹病毒都有共性。第二，包裹机改变了核心机的组织 并为研究该组织提供了一个有用的工具。 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，UL34是单纯疱疹病毒的重要组成部分 包络装置的。我们最初资助期间的结果表明，这种蛋白质发挥作用 至少在包膜的三个方面起关键作用，包括(I)病毒蛋白向核内募集 包膜，(2)防止衣壳接近核的核膜成分的分散 核膜，以及(Iii)核衣壳包裹在核膜中。 这项拟议研究的具体目标有三个 1.我们将通过描述一组七个非功能性的特性来定义UL34蛋白的基本功能 突变的UL34蛋白已经在手中，以及我们将通过保守的突变产生的其他蛋白 残基，因为它们有能力执行包膜所需的各种功能。 2.我们将描述UL34蛋白与其他病毒蛋白之间的关键相互作用 包围圈。这将包括验证UL34介导膜包裹的假设的实验 以及UL34与其他可能参与的病毒蛋白相互作用的筛选 包围圈。 3.我们将充分描述与感染相关的宿主细胞核层的变化，并确定 UL34和其他病毒蛋白完成这些变化的机制。

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.