Bluetongue Virus Morphogenesis

描述(申请人提供)：蓝舌病毒(BTV)是一种多层、 双链节肢动物传播的RNA病毒，是 呼肠孤病毒科的环状病毒。因此，它共享一个病毒家族 与其他几种具有重要科学和医学意义的病毒的关系 例如呼肠孤病毒和轮状病毒。到目前为止，NIH资助的项目 BTV作为一种重要的经济疾病的媒介已被广泛研究 而且，越来越多地，作为整个家族病毒的模型系统。 在序列、生化和大多数方面取得了令人生畏的进展 最近，结构性领域的这种，今天，北京电视台是最好的之一 了解所有的病毒。然而，BTV生物学的某些领域仍然不清楚， 特别是，病毒和宿主蛋白如何共同协调的问题 一个成功的传染病循环。这项建议是为了维持和延长 北京电视台的领先地位，朝着我们的长期目标理解，在 病毒的总体、感染过程和宿主参与其中 无包膜节肢动物传播的病毒。由于其型号状态， 实现BTV的这一目标将使一系列相关病毒受益。这个 提案的重点是四种BTV蛋白，它们在病毒过程中的顺序作用 从病毒进入到离开细胞仍未确定。这个 病毒粒子外衣壳蛋白，VP5，它似乎具有引燃活性和 促进病毒进入细胞质是理解 感染的开始。形成小管的非结构蛋白NS1 (环状病毒独有的)，据信能将病毒粒子组分招募到 复制中心，对富有成效的病毒生命周期至关重要。这个 具有RNA结合能力的磷蛋白NS2在 适当形成的子代病毒粒子的产生，以及NS3与 一种细胞蛋白质，是有效释放病毒的一个因素。的功能 这些蛋白质是BTV生命周期成功的基础 每种蛋白质究竟是如何完成其作用的，以及宿主因素的程度如何 涉案人员在很大程度上仍不为人知。这项建议是建立在我们的成功基础上的 之前的NIH奖，并将利用BTV和相关的广泛范围 由我们的基金支持的试剂。这些基因包括所有BTV基因 克隆、测序和蛋白质表达验证；高度来源 纯化的生物活性BTV蛋白；一系列高滴度的单特异性 抗血清；单抗；序列特异性核酸探针；以及 三维结构信息。连同建议的 实验计划，我们的试剂和知识库将使我们能够 完成我们指定的任务，以提供对病毒的新见解 复制和有效控制的新建议。

DESCRIPTION (provided by applicant): Bluetongue virus (BTV) is a multi-layered, double-stranded, arthropod borne RNA virus and is the type member of the Orbiviruses, within the family Reoviridae. As such it shares a virus family relationship with several other scientifically and medically important viruses such as Reoviruses and Rotaviruses. As a result of NIH funded projects to date BTV has been studied extensively as an agent of economically important disease and also, increasingly, as a model system for viruses of the entire family. Formidable progress has been achieved in sequence, biochemical and most recently, structural fields such that, today, BTV is one of the most well understood of all viruses. Certain areas of BTV biology remain unclear however, in particular, the question of how virus and host protein together orchestrate a successful infectious cycle. This proposal is to maintain and extend the leading position of BTV towards our long term goal of understanding, in totality, the infection course of, and the host involvement with, a non-enveloped arthropod-borne virus. As a result of its model status the achievement of this goal for BTV will benefit a range of related viruses. The proposal focuses on four BTV proteins whose sequential role in viral processes from the entry of the virus to its exit from the cell remain undefined. The virion outer capsid protein, VP5, which appears to have fusigenic activity and facilitate virus entry into the cytoplasm is key to understanding the initiation of infection. The non-structural protein NS 1, that forms tubules (unique to orbiviruses) and is believed to recruit virion components into replication centres, is central to a productive virus life cycle. The phosphoprotein NS2, which has RNA binding ability is crucially important in the generation of appropriately formed progeny virions, and the NS3, together with a cellular protein, is a factor in efficient virus release. The functions of these proteins are fundamental to the success of the BTV life cycle yet precisely how each protein completes its role and to what extent host factors are involved remain largely unknown. The proposal builds on the success of our previous NIH award and will make use the extensive range of BTV and related reagents that have been enabled by our fundings. These include all BTV gene cloned, sequenced and verified by protein expression; sources of highly purified biologically active BTV proteins; a range of high titre monospecific antisera; monoclonal antibodies; sequence specific nucleic acid probes; and three dimensional structural information. Together with the proposed experimental programme, our reagent and knowledge base will allow us to complete the tasks we have specified to offer new insights into virus replication and new suggestions for effective control.