学术预告：Insights into the assembly of the tombusvirusreplicase: the role of co-opted host proteins and lipids
报告题目：Insights into the assembly of the tombusvirusreplicase: the role of co-opted host proteins and lipids
主讲：Peter D. Nagy 教授
Department of Plant Pathology, University of Kentucky Lexington, KY 40546, USA
Peter D. Nagy教授概况：
Peter D. Nagy教授是国际知名的植物病毒学家，他在植物RNA病毒复制、重组及进化的机制研究中获得了许多重要科研成果。他的实验室利用番茄丛矮病毒(TBSV)为模式病毒，开发了利用酵母为模式寄主的研究手段。利用蛋白质组、转录组及脂质组学研究方法及体外生化研究体系，陆续发现了植物病毒复制必须的(pro-viral)或者抗病毒的(anti-viral)的植物寄主因子，包括各类蛋白及特殊脂类。Nagy教授现为
Plus-stranded RNA viruses recruit cellular membranes and subvert cellular proteins involved in lipid biosynthesis to build viral replicase complexes (VRCs) and replication organelles. We use tombusviruses (TBSV), which are small (+)RNA viruses, as model plant viruses to study virus replication, recombination, and virus - host interactions using yeast (Saccharomyces cerevisiae) as a surrogate host. Several systematic genome-wide screens and global proteomic and lipidomic approaches have led to the identification of ~500 host proteins/genes that are implicated in TBSV replication. We characterized the role of a dozen co-opted host proteins, sterols and phosphatidylethanolamine in tombusvirus VRC assembly and viral RNA synthesis. We also present data that Tombusviruses induces the formation of membrane contact sites, where membranes are juxtaposed, to channel lipids to the replication sites. Using in vitro viral replication assay with artificial vesicles, we show stimulation of tombusvirus replication by PE and sterols. Finally, we show evidence that TBSV usurps the ESCRT machinery to form vesicle-like structures to build VRCs in a protected microenvironment involving peroxisomes, early endosomes and ER.