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Journal of Virology, April 2008, p. 3466-3479, Vol. 82, No. 7
0022-538X/08/$08.00+0     doi:10.1128/JVI.02478-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Scavenger Receptor Class B Is Required for Hepatitis C Virus Uptake and Cross-Presentation by Human Dendritic Cells{triangledown}

Heidi Barth,1,2* Eva K. Schnober,1,3,4 Christoph Neumann-Haefelin,1 Christine Thumann,3,5 Mirjam B. Zeisel,3,5 Helmut M. Diepolder,6 Zongyi Hu,2 T. Jake Liang,2 Hubert E. Blum,1 Robert Thimme,1 Mélanie Lambotin,3,5 and Thomas F. Baumert1,3,5,7*

Department of Medicine II, University of Freiburg, Freiburg, Germany,1 Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland,2 Inserm, U748, Strasbourg, France,3 Faculty of Biology, University of Freiburg, Freiburg, Germany,4 Université Louis Pasteur, Strasbourg, France,5 Department of Medicine II, Klinikum Grosshadern, University of Munich, Munich, Germany,6 Service d'Hépatogastroentérologie, Centre Hospitalier Universitaire Strasbourg, Strasbourg, France7

Received 17 November 2007/ Accepted 11 January 2008

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.

* Corresponding author. Mailing address for Heidi Barth: Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892. Phone: (301) 402-5113. Fax: (301) 402-0491. E-mail: barthh{at}niddk.nih.gov. Mailing address for Thomas F. Baumert: Inserm Unit 748, Service d'Hépatogastroentérologie, Université Louis Pasteur, 3 Rue Koeberlé, F-67000 Strasbourg, France. Phone: 33-3 90 24 37 02. Fax: 33-3 90 24 37 23. E-mail: Thomas.Baumert{at}viro-ulp.u-strasbg.fr

{triangledown} Published ahead of print on 23 January 2008.

Journal of Virology, April 2008, p. 3466-3479, Vol. 82, No. 7
0022-538X/08/$08.00+0     doi:10.1128/JVI.02478-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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