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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
Author(s) -
Zeisel Mirjam B.,
Koutsoudakis George,
Schnober Eva K.,
Haberstroh Anita,
Blum Hubert E.,
Cosset FrançoisLoïc,
Wakita Takaji,
Jaeck Daniel,
Doffoel Michel,
Royer Cathy,
Soulier Eric,
Schvoerer Evelyne,
Schuster Catherine,
StollKeller Françoise,
Bartenschlager Ralf,
Pietschmann Thomas,
Barth Heidi,
Baumert Thomas F.
Publication year - 2007
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.21994
Subject(s) - cd81 , scavenger receptor , hepatitis c virus , virology , host factor , biology , antibody , viral entry , epitope , receptor , virus , immunology , lipoprotein , viral replication , cholesterol , endocrinology , biochemistry
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. (H EPATOLOGY 2007.)