RIG: Functional roles of host fatty acyl-CoA binding protein in assembly and function of positive-strand RNA virus replication complexes

RIG：宿主脂肪酰辅酶A结合蛋白在正链RNA病毒复制复合物的组装和功能中的功能作用

• 批准号: 1265260
• 负责人: Xiaofeng Wang
• 金额: $ 12.04万
• 依托单位: Virginia Polytechnic Institute and State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-10-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1265260&HistoricalAwards=false
• 关键词: RIG; Functional; roles; host; fatty

Intellectual Merit. All positive-strand RNA viruses, which include many human, animal and crop pathogens, replicate their RNA genomes on rearranged host intracellular membranes. However, the mechanism whereby these membrane rearrangements are formed is not well defined. The primary objective of the project is to examine the roles of host acyl-CoA binding protein (ACBP) in the assembly and function of viral replication complexes, or viral spherules, of Brome mosaic virus (BMV) using a combination of genetic, biochemical and cell biology approaches. ACBP is highly conserved in all eukaryotes, specifically binds to long chain fatty acyl-CoA, and plays major roles in cellular lipid synthesis. Lack of ACBP severely inhibits BMV replication and results in formation of aberrant viral spherules with a significantly reduced diameter paralleled by a 5-fold increase in frequency compared to those in wild type cells. The specific objectives are: (1). Determining the role of 1a-ACBP interaction in BMV spherule formation and replication. (2). Determining the roles of ACBP in modulating lipid synthesis during BMV replication. The results from this project will better elucidate relations between lipid synthesis and viral replication as well as the microenvironment of the viral replication complexes. Such understanding would advance fundamental knowledge of viral replication mechanisms and virus-host interactions common to positive-strand RNA viruses, and allow identification of potential targets for virus control in humans, animals and plants.Broader impact: ACBP is essential in mammals and this project should stimulate broader interests in testing its roles in replication of human and animal viruses. Besides training a post-doctoral research associate, the PI will continue to involve and train high school and undergraduate students from the Rio Grande Valley (Texas), where more than 85% population are Hispanic.

智力优点。所有阳性链RNA病毒，包括许多人，动物和农作物病原体，在重排的宿主细胞内膜上复制其RNA基因组。但是，这些膜重排的机制尚未很好地定义。该项目的主要目的是使用遗传，生物化学和细胞生物学方法的组合来检查宿主酰基-COA结合蛋白（ACBP）在Brome Mosaic病毒（BMV）的病毒复制复合物或病毒球体的组装或病毒球形的组合中的作用。 ACBP在所有真核生物中都高度保守，特别结合了长链脂肪酰基辅酶A，并且在细胞脂质合成中起着重要作用。缺乏ACBP严重抑制了BMV复制，并导致形成异常的病毒球形，而与野生型细胞相比，直径显着降低，频率增加了5倍。具体目标是：（1）。确定1A-ACBP相互作用在BMV球体形成和复制中的作用。 （2）。确定ACBP在调节BMV复制过程中调节脂质合成的作用。该项目的结果将更好地阐明脂质合成与病毒复制以及病毒复制复合物的微环境之间的关系。这种理解将提高人们对阳性RNA病毒常见的病毒复制机制和病毒宿主相互作用的基本知识，并允许鉴定人类，动物和植物中病毒控制的潜在靶标。除了培训博士后研究助理外，PI还将继续参与和培训来自里奥格兰德山谷（得克萨斯州）的高中和本科生，那里有85％以上的人口是西班牙裔。