title: AP1S3 is required for hepatitis C virus infection by stabilizing E2 protein.
abstract: Hepatitis C virus (HCV) infects 130 million people worldwide and is a leading cause of liver cirrhosis, end-stage liver disease and hepatocellular carcinoma. The interactions between viral elements and host factors play critical role on HCV invade, replication and release. Here, we identified adaptor protein complex 1 sigma 3 subunit (AP1S3) as a dependency factor for the efficient HCV infection in hepatoma cells. AP1S3 silencing in cultivated Huh7.5.1 cells significantly reduced the production of HCV progeny particles. Immunoprecipitation analysis revealed that AP1S3 interacted with the HCV E2 protein. With this interaction, AP1S3 could protect HCV E2 from ubiquitin-mediated proteasomal degradation. Using in vivo ubiquitylation assay, we identified that E6-Associated Protein (E6AP) was associated with HCV E2. In addition, treatment with synthetic peptide that contains the AP1S3-recognized motif inhibited HCV infection in Huh7.5.1 cells. Our data reveal AP1 as a novel host network that is required by viruses during infection and provides a potential target for developing broad-spectrum anti-virus strategies.
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100176, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100176, China.
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Niu
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100176, China.
authors.forename: Min
authors.initials: M
authors.lastname: Cheng
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100176, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Chi
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100176, China.
authors.forename: Xiuying
authors.initials: X
authors.lastname: Liu
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100176, China. Electronic address: wyang@ipb.pumc.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
mesh_terms: D034002:Adaptor Protein Complex sigma Subunits / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000821:virology; D045744:Cell Line, Tumor; D020868:Gene Silencing; D016174:Hepacivirus / Q000187:drug effects / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D047468:Immunoprecipitation; D008113:Liver Neoplasms / Q000821:virology; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012367:RNA, Viral; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism*; D019065:Virus Assembly
chemical_list: C516800:AP1S2 protein, human; D034002:Adaptor Protein Complex sigma Subunits; D010455:Peptides; D012367:RNA, Viral; D025801:Ubiquitin; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex
keywords: AP1S3; E2 glycoprotein; HCV; Protein degradation