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Bluetongue Virus Morphogenesis

蓝舌病毒形态发生

基本信息

批准号：
6897918
负责人：
POLLY ROY
金额：
$ 21.6万
依托单位：
LONDON SCH/HYGIENE & TROPICAL MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-09-28 至 2007-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6897918
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

项目摘要

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，节肢动物携带的RNA病毒，是环状病毒属，呼肠孤病毒科。因此，它共享一个病毒家族与其他几种在科学和医学上具有重要意义的病毒的关系如呼肠孤病毒和轮状病毒。由于NIH迄今为止资助的项目， BTV作为经济上重要的疾病的媒介物已被广泛研究而且，越来越多地，作为整个家族病毒的模型系统。在序列、生物化学和大多数方面都取得了巨大的进展。最近，结构领域，这样，今天，BTV是一个最好的了解所有病毒。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质如何协同一个成功的传染循环这项建议是为了维持和扩大北京电视台的领导地位，对我们的长期目标的理解，总体情况、感染过程和宿主参与，无包膜节肢动物传播病毒。由于其示范地位， BTV这一目标的实现将使一系列相关病毒受益。的一项提案的重点是四种BTV蛋白，它们在病毒过程中的顺序作用从病毒进入细胞到离开细胞的过程仍然不确定。的病毒粒子外衣壳蛋白VP 5似乎具有融合活性，促进病毒进入细胞质是理解感染的开始。非结构蛋白NS 1，形成小管（环状病毒特有的），并被认为是招募病毒体成分进入复制中心是病毒生命周期的核心。的具有RNA结合能力的磷蛋白NS 2在细胞中至关重要。产生适当形成的子代病毒体，和NS 3，以及一种细胞蛋白，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，每种蛋白质如何完成其作用以及宿主因子在多大程度上参与其中的大部分仍不为人知。该提案建立在我们的成功之上。以前的NIH奖，并将利用广泛的BTV和相关的我们的资金支持的试剂。这些包括所有BTV基因克隆、测序并通过蛋白质表达验证; 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;和三维结构信息及说明所建议实验计划，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。