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: 1120598
• 负责人: Xiaofeng Wang
• 金额: $ 19.91万
• 依托单位: Texas A&M Research Foundation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2013-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1120598&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.

智力优势。所有正链RNA病毒，包括许多人类、动物和作物病原体，都在重排的宿主细胞内膜上复制其RNA基因组。然而，这些膜重排形成的机制还没有很好的定义。该项目的主要目的是研究宿主酰基辅酶A结合蛋白（ACBP）在雀麦花叶病毒（BMV）病毒复制复合物或病毒小球组装和功能中的作用，使用遗传学，生物化学和细胞生物学方法相结合。ACBP在所有真核生物中高度保守，特异性结合长链脂肪酰辅酶A，并在细胞脂质合成中起主要作用。缺乏ACBP严重抑制BMV复制，并导致形成直径显著减小的异常病毒小球，与野生型细胞相比，其频率增加5倍。具体目标是：（1）.确定1a-ACBP相互作用在BMV小球形成和复制中的作用。（二）、确定ACBP在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。这样的理解将推进病毒复制机制和病毒-宿主相互作用的基本知识共同的正链RNA病毒，并允许确定潜在的目标，在人类，动物和plants.Broader影响：ACBP是必不可少的哺乳动物和这个项目应该激发更广泛的兴趣，在测试其在人类和动物病毒复制的作用。除了培训博士后研究助理，PI将继续参与和培训高中和本科生从格兰德河谷（得克萨斯州），其中超过85%的人口是西班牙裔。