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. - Archive ouverte HAL Access content directly
Journal Articles Hepatology Year : 2007

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.

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Thomas Pietschmann

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. Conclusion: 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.
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Origin : Files produced by the author(s)
Origin : Files produced by the author(s)
Origin : Files produced by the author(s)
Origin : Files produced by the author(s)
Origin : Files produced by the author(s)
Origin : Files produced by the author(s)
Origin : Files produced by the author(s)
Origin : Files produced by the author(s)
Origin : Files produced by the author(s)

Dates and versions

inserm-00395706 , version 1 (03-11-2009)

Identifiers

Cite

Mirjam B. Zeisel, George Koutsoudakis, Eva K. Schnober, Anita Haberstroh, Hubert E. Blum, et al.. 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.. Hepatology, 2007, 46 (6), pp.1722-31. ⟨10.1002/hep.21994⟩. ⟨inserm-00395706⟩
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