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

✍ Scribed by Mirjam B. Zeisel; George Koutsoudakis; Eva K. Schnober; Anita Haberstroh; Hubert E. Blum; François-Loïc Cosset; Takaji Wakita; Daniel Jaeck; Michel Doffoel; Cathy Royer; Eric Soulier; Evelyne Schvoerer; Catherine Schuster; Françoise Stoll-Keller; Ralf Bartenschlager; Thomas Pietschmann; Heidi Barth; Thomas F. Baumert

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 612 KB
• Volume: 46
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.21994

✦ Synopsis

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. (HEPATOLOGY 2007