title: Scavenger receptor class B is required for hepatitis C virus uptake and cross-presentation by human dendritic cells.
abstract: Class B scavenger receptors (SR-Bs) bind lipoproteins and play an important role in lipid metabolism. Most recently, SR-B type I (SR-BI) and its splicing variant SR-BII have been found to mediate bacterial adhesion and cytosolic bacterial invasion in mammalian cells. In this study, we demonstrate that SR-BI is a key host factor required for hepatitis C virus (HCV) uptake and cross-presentation by human dendritic cells (DCs). Whereas monocytes and T and B cells were characterized by very low or undetectable SR-BI expression levels, human DCs demonstrated a high level of cell surface expression of SR-BI similar to that of primary human hepatocytes. Antibodies targeting the extracellular loop of SR-BI efficiently inhibited HCV-like particle binding, uptake, and cross-presentation by human DCs. Moreover, human high-density lipoprotein specifically modulated HCV-like particle binding to DCs, indicating an interplay of HCV with the lipid transfer function of SR-BI in DCs. Finally, we demonstrate that anti-SR-BI antibodies inhibit the uptake of cell culture-derived HCV (HCVcc) in DCs. In conclusion, these findings identify a novel function of SR-BI for viral antigen uptake and recognition and may have an important impact on the design of HCV vaccines and immunotherapeutic approaches aiming at the induction of efficient antiviral immune responses.
authors.affiliation: Department of Medicine II, University of Freiburg, Freiburg, Germany. barthh@niddk.nih.gov
authors.forename: Heidi
authors.initials: H
authors.lastname: Barth
authors.forename: Eva K
authors.initials: EK
authors.lastname: Schnober
authors.forename: Christoph
authors.initials: C
authors.lastname: Neumann-Haefelin
authors.forename: Christine
authors.initials: C
authors.lastname: Thumann
authors.forename: Mirjam B
authors.initials: MB
authors.lastname: Zeisel
authors.forename: Helmut M
authors.initials: HM
authors.lastname: Diepolder
authors.forename: Zongyi
authors.initials: Z
authors.lastname: Hu
authors.forename: T Jake
authors.initials: TJ
authors.lastname: Liang
authors.forename: Hubert E
authors.initials: HE
authors.lastname: Blum
authors.forename: Robert
authors.initials: R
authors.lastname: Thimme
authors.forename: Mélanie
authors.initials: M
authors.lastname: Lambotin
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Baumert
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001402:B-Lymphocytes / Q000737:chemistry; D002460:Cell Line; D002478:Cells, Cultured; D006224:Cricetinae; D045142:Cross-Priming; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology* / Q000821:virology*; D016174:Hepacivirus / Q000276:immunology* / Q000502:physiology; D022781:Hepatocytes / Q000737:chemistry; D006801:Humans; D007313:Insecta; D009000:Monocytes / Q000737:chemistry; D011991:Receptors, Virus / Q000096:biosynthesis / Q000502:physiology*; D051122:Scavenger Receptors, Class B / Q000096:biosynthesis / Q000502:physiology*; D013601:T-Lymphocytes / Q000737:chemistry; D022701:Virosomes / Q000378:metabolism; D053585:Virus Attachment; D053586:Virus Internalization
chemical_list: D000954:Antigens, Surface; D011991:Receptors, Virus; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D022701:Virosomes