Scavenger receptor class B is required for hepatitis C virus uptake and cross-presentation by human dendritic cells.
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.
Barth
Heidi
H
Department of Medicine II, University of Freiburg, Freiburg, Germany. barthh@niddk.nih.gov
Schnober
Eva K
EK
Neumann-Haefelin
Christoph
C
Thumann
Christine
C
Zeisel
Mirjam B
MB
Diepolder
Helmut M
HM
Hu
Zongyi
Z
Liang
T Jake
TJ
Blum
Hubert E
HE
Thimme
Robert
R
Lambotin
Mélanie
M
Baumert
Thomas F
TF
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
D000954:Antigens, Surface; D011991:Receptors, Virus; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D022701:Virosomes