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.


CONCLUSIONS
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.
Zeisel
Mirjam B
MB
Institut National de la Santé et de la Recherche Médicale (INSERM), U748, Strasbourg, France.
Koutsoudakis
George
G
Schnober
Eva K
EK
Haberstroh
Anita
A
Blum
Hubert E
HE
Cosset
François-Loïc
FL
Wakita
Takaji
T
Jaeck
Daniel
D
Doffoel
Michel
M
Royer
Cathy
C
Soulier
Eric
E
Schvoerer
Evelyne
E
Schuster
Catherine
C
Stoll-Keller
Françoise
F
Bartenschlager
Ralf
R
Pietschmann
Thomas
T
Barth
Heidi
H
Baumert
Thomas F
TF
D015703:Antigens, CD / Q000276:immunology*; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016174:Hepacivirus; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D051122:Scavenger Receptors, Class B / Q000276:immunology*; D060225:Tetraspanin 28
D015703:Antigens, CD; C554798:CD81 protein, human; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D060225:Tetraspanin 28