title: Comparative Proteomics Reveals Important Viral-Host Interactions in HCV-Infected Human Liver Cells.
abstract: Hepatitis C virus (HCV) poses a global threat to public health. HCV envelop protein E2 is the major component on the virus envelope, which plays an important role in virus entry and morphogenesis. Here, for the first time, we affinity purified E2 complex formed in HCV-infected human hepatoma cells and conducted comparative mass spectrometric analyses. 85 cellular proteins and three viral proteins were successfully identified in three independent trials, among which alphafetoprotein (AFP), UDP-glucose: glycoprotein glucosyltransferase 1 (UGT1) and HCV NS4B were further validated as novel E2 binding partners. Subsequent functional characterization demonstrated that gene silencing of UGT1 in human hepatoma cell line Huh7.5.1 markedly decreased the production of infectious HCV, indicating a regulatory role of UGT1 in viral lifecycle. Domain mapping experiments showed that HCV E2-NS4B interaction requires the transmembrane domains of the two proteins. Altogether, our proteomics study has uncovered key viral and cellular factors that interact with E2 and provided new insights into our understanding of HCV infection.
authors.affiliation: Center for Immunology and Infectious Diseases, Bioscience Division, SRI International, Harrisonburg, Virginia, 22802, United States of America.
authors.forename: Shufeng
authors.initials: S
authors.lastname: Liu
authors.affiliation: College of Pharmacy, University of Michigan, Ann Arbor, Michigan, 48109, United States of America.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhao
authors.affiliation: SLS Global Technical Support, Pall Corporation, Port Washington, New York, 11050, United States of America.
authors.forename: BenBen
authors.initials: B
authors.lastname: Song
authors.affiliation: Department of Urology, School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, 15232, United States of America.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Center for Immunology and Infectious Diseases, Bioscience Division, SRI International, Harrisonburg, Virginia, 22802, United States of America.
authors.forename: Tony T
authors.initials: TT
authors.lastname: Wang
mesh_terms: D014453:Glucuronosyltransferase / Q000378:metabolism; D057809:HEK293 Cells; D016174:Hepacivirus / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000821:virology*; D040901:Proteomics; D053719:Tandem Mass Spectrometry; D017361:Viral Nonstructural Proteins / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: C080107:NS4B protein, flavivirus; D017361:Viral Nonstructural Proteins; D000509:alpha-Fetoproteins; D014453:Glucuronosyltransferase