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

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.