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 Dec;46(6):1722-31. doi: 10.1002/hep.21994.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / immunology*
  • Carcinoma, Hepatocellular
  • Cell Line, Tumor
  • Cells, Cultured
  • Hepacivirus
  • Hepatitis C / immunology*
  • Humans
  • Scavenger Receptors, Class B / immunology*
  • Tetraspanin 28


  • Antigens, CD
  • CD81 protein, human
  • SCARB1 protein, human
  • Scavenger Receptors, Class B
  • Tetraspanin 28