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Phosphatidylserine-Specific Phospholipase A1 is the Critical Bridge for Hepatitis C Virus Assembly

查看全文 作　　者：Qi [1,2]Yang;Min [3]Guo;Yuan [2]Zhou;Xue [2]Hu;Yun [2]Wang;Chunchen [2]Wu;Min [1]Yang;Rongjuan [2]Pei;Xinwen [2]Chen;Jizheng [2]Chen 高影响力作者 机构地区：[1]Department of Gastroenterology,Guangzhou Women and Children's Medical Center,Guangzhou 510623,China;[2]State Key Laboratory of Virology,Wuhan Institute of Virology,Chinese Academy of Sciences,Wuhan 430071,China;[3]School of Life Science and Technology,China Pharmaceutical University,Nanjing 210009,China高影响力机构 出　　处：《Virologica Sinica》索引2019年第34卷第5期,共17页高影响力期刊 基　　金：supported by grants of the National Basic Research Priorities Program of China (2015CB554304) 摘　　要：The phosphatidylserine-specific phospholipase A1(PLA1A)is an essential host factor in hepatitis C virus(HCV)assembly.In this study,we mapped the E2,NS2 and NS5A involved in PLA1A interaction to their lumenal domains and membranous parts,through which they form oligomeric protein complexes to participate in HCV assembly.Multiple regions of PLA1A were involved in their interaction and complex formation.Furthermore,the results represented structures with PLA1A and E2 in closer proximity than NS2 and NS5A,and strongly suggest PLA1 A-E2,s physical interaction in cells.Meanwhile,we mapped the NS5A sequence which participated in PLA1A interaction with the C-terminus of domain 1.Interestingly,these amino acids in the sequence are also essential for viral RNA replication.Further experiments revealed that these four proteins interact with each other.Moreover,PLA1A expression levels were elevated in livers from HCV-infected patients.In conclusion,we exposed the structural determinants of PLA1A,E2,NS2 and NS5A proteins which were important for HCV assembly and provided a detailed characterization of PLA1A in HCV assembly. 关 键 词：Phosphatidylserine-specific phospholipase A1(PLA1 A) HCV assembly Viral RNA replication
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