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）：蓝光病毒（BTV）是多层 双链，节肢动物传播RNA病毒，是该类型的成员 Orbiviruses，在家族中。因此，它有一个病毒家庭 与其他科学和医学重要的病毒的关系 例如蠕虫病毒和轮状病毒。由于NIH资助的项目迄今 BTV已被广泛研究为经济上重要疾病的推动者 而且，越来越多地是整个家庭病毒的模型系统。 序列，生化和大多数取得了巨大的进步 最近，结构领域，如今，BTV是最井的结构领域之一 了解所有病毒。 BTV生物学的某些领域仍不清楚，但是 特别是，病毒和宿主蛋白如何编排的问题 成功的感染周期。该建议是维护和扩展 BTV朝着我们的长期理解目标的领先地位 总体，感染过程以及宿主参与 非发育节肢动物传播病毒。由于其模型状态 实现BTV目标将使一系列相关病毒受益。这 提案重点关注四种BTV蛋白，其顺序在病毒过程中作用 从病毒的进入到其从细胞退出，仍然不确定。这 Virion Capsid蛋白，VP5，似乎具有熔融活性和 促进病毒进入细胞质是理解的关键 启动感染。形成小管的非结构蛋白NS 1 （Orbiviruses独有），并且被认为可以将病毒粒子组件招募到 复制中心是生产性病毒生命周期的核心。这 具有RNA结合能力的磷蛋白NS2在至关重要的 生成适当形成的后代病毒体和NS3 细胞蛋白是有效病毒释放的因素。功能 这些蛋白质对BTV生命周期的成功至关重要 确切地，每种蛋白质如何完成其​​作用以及宿主因素在多大程度上 涉及的依据在很大程度上未知。该提案以我们的成功为基础 以前的NIH奖，将利用大量的BTV和相关性 我们的资金启用的试剂。这些包括所有BTV基因 克隆，测序和通过蛋白质表达进行验证；高度来源 纯化的生物活性BTV蛋白；一系列高滴度单特异性 安塞拉;单克隆抗体；序列特异性核酸探针；和 三维结构信息。和拟议的 实验计划，我们的试剂和知识基础将使我们能够 完成我们指定的任务，以提供有关病毒的新见解 复制和有效控制的新建议。