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

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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.