Scavenger receptor class B is required for hepatitis C virus uptake and cross-presentation by human dendritic cells

Heidi Barth, Eva K. Schnober, Christoph Neumann-Haefelin, Christine Thumann, Mirjam B. Zeisel, Helmut M. Diepolder, Zongyi Hu, T. Jake Hang, Hubert E. Blum, Robert Thimme, Mélanie Lambotin, Thomas F. Baumert

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)3466-3479
Number of pages14
JournalJournal of Virology
Volume82
Issue number7
DOIs
Publication statusPublished - Apr 2008
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

Cite this

Barth, H., Schnober, E. K., Neumann-Haefelin, C., Thumann, C., Zeisel, M. B., Diepolder, H. M., ... Baumert, T. F. (2008). Scavenger receptor class B is required for hepatitis C virus uptake and cross-presentation by human dendritic cells. Journal of Virology, 82(7), 3466-3479. https://doi.org/10.1128/JVI.02478-07