UL34 and herpes simplex virus envelopment

疱疹病毒在细胞核中复制和包装它们的基因组。为了开始它的进程 病毒要逃离细胞，必须首先通过核膜进入细胞内部 核膜在一个叫做初级分裂的过程中。疱疹病毒的免疫机制是 从两个方面来看，对人体健康有重要意义。首先，这一进程是一个有吸引力的目标， 治疗，因为它在许多方面与病毒所必需的任何正常细胞过程不同， 所有疱疹病毒都有第二，核反应器的结构发生了变化， 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UL 34的研究基础上， 的设备。我们最初的研究结果表明这种蛋白质 至少在三个方面起着关键作用，包括（i）将病毒蛋白募集到细胞核中 （ii）阻止衣壳进入核被膜的核膜成分的分散 膜，和（iii）核衣壳在核膜中的包裹。 拟议研究的具体目标有三个方面 1.我们将通过表征一组七个非功能性的蛋白质来定义UL 34蛋白的基本功能。 突变的UL 34蛋白已经在手，和其他人，我们将产生的保守的突变的UL 34蛋白， 残基，因为它们的能力，以执行所需的各种功能，以消除。 2.我们将描述UL 34蛋白和其他病毒蛋白之间的关键相互作用， - 谢谢这将包括实验，以测试的假设，即UL 34介导膜包裹 以及筛选UL 34与其他可能参与 - 谢谢 3.我们将充分描述与感染相关的宿主细胞核纤层的变化，并确定 UL 34和其他病毒蛋白实现这些变化的机制。

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.