title: Apolipoprotein E interacts with hepatitis C virus nonstructural protein 5A and determines assembly of infectious particles.
abstract: Chronic hepatitis C virus (HCV) infection is a major cause of liver disease worldwide. Restriction of HCV infection to human hepatocytes suggests that liver-specific host factors play a role in the viral life cycle. Using a yeast-two-hybrid system, we identified apolipoprotein E (apoE) as a liver-derived host factor specifically interacting with HCV nonstructural protein 5A (NS5A) but not with other viral proteins. The relevance of apoE-NS5A interaction for viral infection was confirmed by co-immunoprecipitation and co-localization studies of apoE and NS5A in an infectious HCV cell culture model system. Silencing apoE expression resulted in marked inhibition of infectious particle production without affecting viral entry and replication. Analysis of particle production in liver-derived cells with silenced apoE expression showed impairment of infectious particle assembly and release. The functional relevance of the apoE-NS5A interaction for production of viral particles was supported by loss or decrease of apoE-NS5A binding in assembly-defective viral mutants.
  
  
  CONCLUSIONS
  These results suggest that recruitment of apoE by NS5A is important for viral assembly and release of infectious viral particles. These findings have important implications for understanding the HCV life cycle and the development of novel antiviral strategies targeting HCV-lipoprotein interaction.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) Unite 748, Strasbourg, France.
authors.forename: Wagane J A
authors.initials: WJ
authors.lastname: Benga
authors.forename: Sophie E
authors.initials: SE
authors.lastname: Krieger
authors.forename: Maria
authors.initials: M
authors.lastname: Dimitrova
authors.forename: Mirjam B
authors.initials: MB
authors.lastname: Zeisel
authors.forename: Marie
authors.initials: M
authors.lastname: Parnot
authors.forename: Joachim
authors.initials: J
authors.lastname: Lupberger
authors.forename: Eberhard
authors.initials: E
authors.lastname: Hildt
authors.forename: Guangxiang
authors.initials: G
authors.lastname: Luo
authors.forename: John
authors.initials: J
authors.lastname: McLauchlan
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Baumert
authors.forename: Catherine
authors.initials: C
authors.lastname: Schuster
mesh_terms: D001057:Apolipoproteins E / Q000378:metabolism*; D045744:Cell Line, Tumor; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D020798:Two-Hybrid System Techniques; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D001057:Apolipoproteins E; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase