title: Phosphatidylserine-specific phospholipase A1 involved in hepatitis C virus assembly through NS2 complex formation.
abstract: Several members of the phospholipase family have been reported to be involved in hepatitis C virus (HCV) replication. Here, we identified another phospholipase, phosphatidylserine-specific phospholipase A1 (PLA1A), as a host factor involved in HCV assembly. PLA1A was upregulated by HCV infection, and PLA1A knockdown significantly reduced J399EM (genotype 2a) HCV propagation at the assembly step but not the entry, RNA replication, and protein translation steps of the life cycle. Protein localization and interaction analysis further revealed a role of PLA1A in the interaction of NS2-E2 and NS2-NS5A, as the formation of the NS2-E2 and NS2-NS5A complexes was weakened in the absence of PLA1A. In addition, PLA1A stabilized the NS2/NS5A dotted structure during infection. These data suggest that PLA1A plays an important role in bridging the membrane-associated NS2-E2 complex and the NS5A-associated replication complex via its interaction with E2, NS2, and NS5A, which leads to a coordinating interaction between the structural and nonstructural proteins and facilitates viral assembly.
  
  
  OBJECTIVE
  Hepatitis C virus (HCV) genomic replication is driven by the replication complex and occurs at the membranous web, while the lipid droplet is the organelle in which virion assembly is initiated. In this study, we identified phosphatidylserine-specific phospholipase A1 (PLA1A), a member of phospholipase A 1 family, as a novel host factor involved in the assembly process of HCV. PLA1A, which is induced by HCV infection at a late infection stage, interacts with HCV E2, NS2, and NS5A proteins and enhances and stabilizes the NS2-E2 and NS2-NS5A complex formation, which is essential for viral assembly. Thus, PLA1A is an important host factor which is involved in the initiation of the viral assembly in close proximity to Core-decorated lipid droplets through bringing together the HCV replication complex and envelope complex.
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China rongjuan_pei@wh.iov.cn chenxw@wh.iov.cn.
authors.forename: Rongjuan
authors.initials: R
authors.lastname: Pei
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Huang
authors.initials: H
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Chunchen
authors.initials: C
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Jizheng
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Infectious Disease, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Mengji
authors.initials: M
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China rongjuan_pei@wh.iov.cn chenxw@wh.iov.cn.
authors.forename: Xinwen
authors.initials: X
authors.lastname: Chen
mesh_terms: D002460:Cell Line; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D016174:Hepacivirus / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D054466:Phospholipases A1 / Q000378:metabolism*; D055503:Protein Multimerization; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D019065:Virus Assembly
chemical_list: C097010:NS2 protein, Hepatitis C virus; D017361:Viral Nonstructural Proteins; C512665:PLA1A protein, human; D054466:Phospholipases A1