Bluetongue Virus Morphogenesis

蓝舌病毒形态发生

• 批准号: 6646495
• 负责人: POLLY ROY
• 金额: $ 28.7万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-28 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6646495
• 关键词: Orbivirus; capsid; chimeric proteins; gene mutation; host organism interaction; intermolecular interaction; molecular cloning; nucleocapsid; protein structure function; site directed mutagenesis; tissue /cell culture; virion; virus RNA; virus infection mechanism; virus protein; yeast two hybrid system

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.

描述（由申请人提供）：蓝舌病毒（BTV）是一种多层、 双链、节肢动物传播的 RNA 病毒，是该病毒的模式成员 环状病毒属，属于呼肠孤病毒科。因此它共享一个病毒家族 与其他几种具有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。迄今为止 NIH 资助的项目的结果 BTV 作为经济上重要疾病的媒介已被广泛研究 并且也越来越多地作为整个病毒家族的模型系统。 在序列、生化和大多数方面已经取得了巨大的进展。 最近，结构领域如此，今天，BTV 是最好的之一 了解所有病毒。然而，BTV 生物学的某些领域仍不清楚， 特别是病毒和宿主蛋白如何共同协调的问题 一个成功的感染周期。该提案旨在维持和扩展 BTV 在实现我们理解的长期目标方面处于领先地位， 总体、感染过程以及宿主参与 无包膜节肢动物传播的病毒。由于其型号地位 BTV这一目标的实现将使一系列相关病毒受益。这 提案重点关注四种 BTV 蛋白，它们在病毒过程中发挥连续作用 从病毒进入细胞到退出细胞的整个过程仍不清楚。这 病毒体外衣壳蛋白 VP5，似乎具有融合活性 促进病毒进入细胞质是理解病毒的关键 感染的开始。形成肾小管的非结构蛋白 NS 1 （环状病毒所独有），据信可将病毒粒子成分招募到 复制中心是高效病毒生命周期的核心。这 磷蛋白 NS2 具有 RNA 结合能力，在 产生适当形成的子代病毒体和 NS3，以及 一种细胞蛋白，是病毒有效释放的一个因素。的功能 这些蛋白质是 BTV 生命周期成功的基础 每种蛋白质到底如何完成其​​作用以及宿主因素在多大程度上发挥作用 所涉及的情况在很大程度上仍然未知。该提案建立在我们的成功基础上 之前的 NIH 奖项，并将利用 BTV 和相关的广泛范围 我们的资金支持的试剂。这些包括所有BTV基因 通过蛋白质表达进行克隆、测序和验证；高的来源 纯化的生物活性 BTV 蛋白；一系列高滴度单特异性 抗血清；单克隆抗体；序列特异性核酸探针；和 三维结构信息。连同提议的 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。