title: Scavenger receptor class B type I is a key host factor for hepatitis C virus infection required for an entry step closely linked to CD81.
abstract: Hepatitis C virus (HCV) is a major cause of chronic hepatitis worldwide. Scavenger receptor class B type I (SR-BI) has been shown to bind HCV envelope glycoprotein E2, participate in entry of HCV pseudotype particles, and modulate HCV infection. However, the functional role of SR-BI for productive HCV infection remains unclear. In this study, we investigated the role of SR-BI as an entry factor for infection of human hepatoma cells using cell culture-derived HCV (HCVcc). Anti-SR-BI antibodies directed against epitopes of the human SR-BI extracellular loop specifically inhibited HCVcc infection in a dose-dependent manner. Down-regulation of SR-BI expression by SR-BI-specific short interfering RNAs (siRNAs) markedly reduced the susceptibility of human hepatoma cells to HCVcc infection. Kinetic studies demonstrated that SR-BI acts predominately after binding of HCV at an entry step occurring at a similar time point as CD81-HCV interaction. Although the addition of high-density lipoprotein (HDL) enhanced the efficiency of HCVcc infection, anti-SR-BI antibodies and SR-BI-specific siRNA efficiently inhibited HCV infection independent of lipoprotein.
  
  
  CONCLUSIONS
  Our data suggest that SR-BI (i) represents a key host factor for HCV entry, (ii) is implicated in the same HCV entry pathway as CD81, and (iii) targets an entry step closely linked to HCV-CD81 interaction.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U748, Strasbourg, France.
authors.forename: Mirjam B
authors.initials: MB
authors.lastname: Zeisel
authors.forename: George
authors.initials: G
authors.lastname: Koutsoudakis
authors.forename: Eva K
authors.initials: EK
authors.lastname: Schnober
authors.forename: Anita
authors.initials: A
authors.lastname: Haberstroh
authors.forename: Hubert E
authors.initials: HE
authors.lastname: Blum
authors.forename: François-Loïc
authors.initials: FL
authors.lastname: Cosset
authors.forename: Takaji
authors.initials: T
authors.lastname: Wakita
authors.forename: Daniel
authors.initials: D
authors.lastname: Jaeck
authors.forename: Michel
authors.initials: M
authors.lastname: Doffoel
authors.forename: Cathy
authors.initials: C
authors.lastname: Royer
authors.forename: Eric
authors.initials: E
authors.lastname: Soulier
authors.forename: Evelyne
authors.initials: E
authors.lastname: Schvoerer
authors.forename: Catherine
authors.initials: C
authors.lastname: Schuster
authors.forename: Françoise
authors.initials: F
authors.lastname: Stoll-Keller
authors.forename: Ralf
authors.initials: R
authors.lastname: Bartenschlager
authors.forename: Thomas
authors.initials: T
authors.lastname: Pietschmann
authors.forename: Heidi
authors.initials: H
authors.lastname: Barth
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Baumert
mesh_terms: D015703:Antigens, CD / Q000276:immunology*; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016174:Hepacivirus; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D051122:Scavenger Receptors, Class B / Q000276:immunology*; D060225:Tetraspanin 28
chemical_list: D015703:Antigens, CD; C554798:CD81 protein, human; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D060225:Tetraspanin 28