High-density lipoproteins reduce the neutralizing effect of hepatitis C virus (HCV)-infected patient antibodies by promoting HCV entry

• Published in: Journal of general virology 2006-09, Vol.87 (9), p.2577-2581
• Main Authors: Voisset, Cecile, de Beeck, Anne Op, Horellou, Pauline, Dreux, Marlene, Gustot, Thierry, Duverlie, Gilles, Cosset, Francois-Loic, Vu-Dac, Ngoc, Dubuisson, Jean
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal - immunology; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Hepacivirus - pathogenicity; Hepacivirus - physiology; Hepatitis C - blood; Hepatitis C - immunology; Hepatitis C - virology; Hepatitis C Antibodies - immunology; Hepatitis C virus; Humans; In Vitro Techniques; Life Sciences; Lipoproteins, HDL - immunology; Lipoproteins, HDL - physiology; Microbiology; Microbiology and Parasitology; Miscellaneous; Neutralization Tests; Scavenger Receptors, Class B - physiology; Virology
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/vir.0.81932-0

1 CNRS, Institut de Biologie de Lille (UMR8161), Institut Pasteur de Lille, 1 rue Calmette, BP447, 59021 Lille cedex, France 2 Free University of Brussels, Faculty of Medicine, Laboratory of Molecular Virology, Brussels, Belgium 3 INSERM-U412, ENS de Lyon, Lyon, France 4 Hôpital Erasme, Free University of Brussels, Brussels, Belgium 5 Laboratory of Virology, Centre Hospitalier Universitaire d'Amiens, Amiens, France Correspondence Ngoc Vu-Dac ngoc.vu-dac{at}ibl.fr 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.