The interaction of natural hepatitis C virus with human scavenger receptor SR-BI/Cla1 is mediated by ApoB-containing lipoproteins.
The possible role of candidate receptors in the cellular penetration of HCV from serum of infected patients remains unclear. SR-BI/Cla1 interacts with plasma HDL, native and modified LDL, and VLDL, and facilitates cellular cholesterol efflux to lipoprotein acceptors. SR-BI/Cla1 binds HCV E2 protein and interacts with HCV pseudotypes via the HVR1 of the E2 envelope glycoprotein. Our data reveal that functional SR-BI/Cla1 expressed on the surface of CHO cells mediates the binding and uptake of HCV from the sera of infected patients. Interaction between HCV and SR-BI/Cla1 is not sensitive to either anti-E2 or anti-HVR1 antibodies but is effectively inhibited by anti-betalipoprotein antibodies and competed out by apoB-containing lipoproteins and notably by VLDL. We interpret our data to indicate that VLDL associated with or incorporated into HCV plays a critical role in the primary interaction of HCV with SR-BI/Cla1, whereas the HCV E2 protein does not. In addition, our findings in hepatoma cell lines suggest that the interaction of HCV with human hepatocytes is equally mediated, at least in a part, by VLDL, and as such may represent an alternative pathway for infection. The association of HCV with ApoB-containing lipoproteins may promote cellular uptake of this virus in the presence of neutralizing antibodies.
Hepacivirus Unit, Pasteur Institute, Paris, France.
Patrick
P
Maillard
Thierry
T
Huby
Ursula
U
Andréo
Martine
M
Moreau
John
J
Chapman
Agata
A
Budkowska
D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism*; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D005786:Gene Expression Regulation; D016174:Hepacivirus / Q000378:metabolism*; D006801:Humans; D051122:Scavenger Receptors, Class B / Q000378:metabolism*
D001055:Apolipoproteins B; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B