title: Quantitative Lipid Droplet Proteome Analysis Identifies Annexin A3 as a Cofactor for HCV Particle Production.
abstract: Lipid droplets are vital to hepatitis C virus (HCV) infection as the putative sites of virion assembly, but morphogenesis and egress of virions remain ill defined. We performed quantitative lipid droplet proteome analysis of HCV-infected cells to identify co-factors of that process. Our results demonstrate that HCV disconnects lipid droplets from their metabolic function. Annexin A3 (ANXA3), a protein enriched in lipid droplet fractions, strongly impacted HCV replication and was characterized further: ANXA3 is recruited to lipid-rich fractions in HCV-infected cells by the viral core and NS5A proteins. ANXA3 knockdown does not affect HCV RNA replication but severely impairs virion production with lower specific infectivity and higher density of secreted virions. ANXA3 is essential for the interaction of viral envelope E2 with apolipoprotein E (ApoE) and for trafficking, but not lipidation, of ApoE in HCV-infected cells. Thus, we identified ANXA3 as a regulator of HCV maturation and egress.
authors.affiliation: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Rösch
authors.affiliation: Core Facility Mass Spectrometric Proteomics, Institute of Clinical Chemistry, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Kwiatkowski
authors.affiliation: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hofmann
authors.affiliation: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Schöbel
authors.affiliation: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany.
authors.forename: Cordula
authors.initials: C
authors.lastname: Grüttner
authors.affiliation: Core Facility Mass Spectrometric Proteomics, Institute of Clinical Chemistry, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Wurlitzer
authors.affiliation: Core Facility Mass Spectrometric Proteomics, Institute of Clinical Chemistry, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Schlüter
authors.affiliation: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany. Electronic address: eva.herker@hpi.uni-hamburg.de.
authors.forename: Eva
authors.initials: E
authors.lastname: Herker
mesh_terms: D017318:Annexin A3 / Q000378:metabolism*; D002460:Cell Line; D016174:Hepacivirus / Q000502:physiology*; D006790:Host-Parasite Interactions / Q000502:physiology*; D006801:Humans; D066292:Lipid Droplets / Q000378:metabolism / Q000821:virology*; D020543:Proteome / Q000032:analysis; D040901:Proteomics; D019065:Virus Assembly / Q000502:physiology*
chemical_list: D020543:Proteome; D017318:Annexin A3