title: Quantitative Proteomics Identifies Serum Response Factor Binding Protein 1 as a Host Factor for Hepatitis C Virus Entry.
abstract: Hepatitis C virus (HCV) enters human hepatocytes through a multistep mechanism involving, among other host proteins, the virus receptor CD81. How CD81 governs HCV entry is poorly characterized, and CD81 protein interactions after virus binding remain elusive. We have developed a quantitative proteomics protocol to identify HCV-triggered CD81 interactions and found 26 dynamic binding partners. At least six of these proteins promote HCV infection, as indicated by RNAi. We further characterized serum response factor binding protein 1 (SRFBP1), which is recruited to CD81 during HCV uptake and supports HCV infection in hepatoma cells and primary human hepatocytes. SRFBP1 facilitates host cell penetration by all seven HCV genotypes, but not of vesicular stomatitis virus and human coronavirus. Thus, SRFBP1 is an HCV-specific, pan-genotypic host entry factor. These results demonstrate the use of quantitative proteomics to elucidate pathogen entry and underscore the importance of host protein-protein interactions during HCV invasion.
authors.affiliation: Insitute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, 30165 Hannover, Germany; Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, the Rockefeller University, New York, NY 10065, USA. Electronic address: gisa.gerold@twincore.de.
authors.forename: Gisa
authors.initials: G
authors.lastname: Gerold
authors.affiliation: Department of Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, 82152 Martinsried, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Meissner
authors.affiliation: Insitute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, 30165 Hannover, Germany.
authors.forename: Janina
authors.initials: J
authors.lastname: Bruening
authors.affiliation: Insitute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, 30165 Hannover, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Welsch
authors.affiliation: Insitute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, 30165 Hannover, Germany.
authors.forename: Paula M
authors.initials: PM
authors.lastname: Perin
authors.affiliation: Inserm Unit 1110, Université de Strasbourg, Strasbourg 67000, France.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Baumert
authors.affiliation: Department of General, Visceral and Transplant Surgery, Hannover Medical School, 30165 Hannover, Germany.
authors.forename: Florian W
authors.initials: FW
authors.lastname: Vondran
authors.affiliation: Institute for Medical Informatics and Biometry (IMB), Medical School, University of Technology Dresden, 01307 Dresden, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Kaderali
authors.affiliation: Center for Advanced Biotechnology and Medicine, Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Marcotrigiano
authors.affiliation: Center for Advanced Biotechnology and Medicine, Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Abdul G
authors.initials: AG
authors.lastname: Khan
authors.affiliation: Department of Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, 82152 Martinsried, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
authors.affiliation: Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, the Rockefeller University, New York, NY 10065, USA.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rice
authors.affiliation: Insitute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, 30165 Hannover, Germany. Electronic address: thomas.pietschmann@twincore.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pietschmann
mesh_terms: D045744:Cell Line, Tumor; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D040901:Proteomics; D014157:Transcription Factors / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: C496545:SRFBP1 protein, human; D014157:Transcription Factors