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

智力上的功绩。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它们的RNA基因组。然而，这些膜重排形成的机制还没有很好地确定。该项目的主要目标是利用遗传学、生物化学和细胞生物学相结合的方法，研究宿主酰基-辅酶A结合蛋白(ACBP)在雀麦花叶病毒(BMV)病毒复制复合体或病毒球体组装和功能中的作用。ACBP在所有真核生物中高度保守，与长链脂肪酰辅酶A特异性结合，在细胞脂质合成中发挥重要作用。缺乏ACBP会严重抑制BMV的复制，并导致异常病毒球体的形成，与野生型细胞相比，直径明显减小，频率增加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和病毒复制之间的关系，以及病毒复制复合体的微环境。这样的理解将促进对正链RNA病毒常见的病毒复制机制和病毒与宿主相互作用的基础知识，并有助于确定在人类、动物和植物中控制病毒的潜在靶点。广泛影响：ACBP在哺乳动物中是必不可少的，该项目应该会激发更广泛的兴趣，测试它在人和动物病毒复制中的作用。除了培训一名博士后助理研究员外，PI还将继续参与和培训来自里奥格兰德山谷(德克萨斯州)的高中生和本科生，那里的人口超过85%是西班牙裔。

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.