High-density lipoproteins reduce the neutralizing effect of hepatitis C virus (HCV)-infected patient antibodies by promoting HCV entry.
The neutralizing activity of anti-hepatitis C virus (HCV) antibodies is attenuated by a factor present in human sera, which has been proposed to be high-density lipoproteins (HDLs). HDLs have also been shown to facilitate the entry of HCV pseudoparticles (HCVpp) into target cells. Here, the aim of the study was to determine whether HDL-mediated facilitation of HCVpp and infectious HCV (HCVcc) entry and attenuation of neutralization are two related phenomena. The data indicated that HDLs attenuate neutralization at a constant rate. In addition, as for HDL-mediated facilitation of HCVpp entry, attenuation of neutralization depended on the expression of the scavenger receptor BI (SR-BI) and its selective lipid-uptake function. Finally, kinetic experiments showed that HDL-mediated facilitation of HCVpp entry is more rapid than virus neutralization. Altogether, these observations indicate that HCV is exploiting the physiological activity of SR-BI for promoting its entry into target cells, which consequently also protects the virus against neutralizing antibodies.
Voisset
Cécile
C
CNRS, Institut de Biologie de Lille (UMR8161), Institut Pasteur de Lille, 1 rue Calmette, BP447, 59021 Lille cedex, France.
de Beeck
Anne Op
AO
Free University of Brussels, Faculty of Medicine, Laboratory of Molecular Virology, Brussels, Belgium.|CNRS, Institut de Biologie de Lille (UMR8161), Institut Pasteur de Lille, 1 rue Calmette, BP447, 59021 Lille cedex, France.
Horellou
Pauline
P
CNRS, Institut de Biologie de Lille (UMR8161), Institut Pasteur de Lille, 1 rue Calmette, BP447, 59021 Lille cedex, France.
Dreux
Marlène
M
INSERM-U412, ENS de Lyon, Lyon, France.
Gustot
Thierry
T
Hôpital Erasme, Free University of Brussels, Brussels, Belgium.
Duverlie
Gilles
G
Laboratory of Virology, Centre Hospitalier Universitaire d'Amiens, Amiens, France.|CNRS, Institut de Biologie de Lille (UMR8161), Institut Pasteur de Lille, 1 rue Calmette, BP447, 59021 Lille cedex, France.
Cosset
François-Loic
FL
INSERM-U412, ENS de Lyon, Lyon, France.
Vu-Dac
Ngoc
N
CNRS, Institut de Biologie de Lille (UMR8161), Institut Pasteur de Lille, 1 rue Calmette, BP447, 59021 Lille cedex, France.
Dubuisson
Jean
J
CNRS, Institut de Biologie de Lille (UMR8161), Institut Pasteur de Lille, 1 rue Calmette, BP447, 59021 Lille cedex, France.
D000911:Antibodies, Monoclonal / Q000276:immunology; D016174:Hepacivirus / Q000472:pathogenicity* / Q000502:physiology; D006526:Hepatitis C / Q000097:blood / Q000276:immunology / Q000821:virology; D018937:Hepatitis C Antibodies / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D008075:Lipoproteins, HDL / Q000276:immunology / Q000502:physiology*; D009500:Neutralization Tests; D051122:Scavenger Receptors, Class B / Q000502:physiology
D000911:Antibodies, Monoclonal; D018937:Hepatitis C Antibodies; D008075:Lipoproteins, HDL; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B