High-avidity monoclonal antibodies against the human scavenger class B type I receptor efficiently block hepatitis C virus infection in the presence of high-density lipoprotein.

Abstract

The human scavenger class B type 1 receptor (SR-B1/Cla1) was identified as a putative receptor for hepatitis C virus (HCV) because it binds to soluble recombinant HCV envelope glycoprotein E2 (sE2). High-density lipoprotein (HDL), a natural SR-B1 ligand, was shown to increase the in vitro infectivity of retroviral pseudoparticles bearing HCV envelope glycoproteins and of cell culture-derived HCV (HCVcc), suggesting that SR-B1 promotes viral entry in an HDL-dependent manner. To determine whether SR-B1 participates directly in HCV infection or facilitates HCV entry through lipoprotein uptake, we generated a panel of monoclonal antibodies (MAbs) against native human SR-B1. Two of them, 3D5 and C167, bound to conformation-dependent SR-B1 determinants and inhibited the interaction of sE2 with SR-B1. These antibodies efficiently blocked HCVcc infection of Huh-7.5 hepatoma cells in a dose-dependent manner. To examine the role of HDL in SR-B1-mediated HCVcc infection, we set up conditions for HCVcc production and infection in serum-free medium. HCVcc efficiently infected Huh-7.5 cells in the absence of serum lipoproteins, and addition of HDL led to a twofold increase in infectivity. However, the HDL-induced enhancement of infection had no impact on the neutralization potency of MAb C167, despite its ability to inhibit both HDL binding to cells and SR-B1-mediated lipid transfer. Of note, MAb C167 also potently blocked Huh-7.5 infection by an HCV strain recovered from HCVcc-infected chimpanzees. These results demonstrate that SR-B1 is essential for infection with HCV produced in vitro and in vivo and suggest the possible use of anti-SR-B1 antibodies as therapeutic agents.

• Authors: Maria Teresa Catanese, Rita Graziani, Thomas von Hahn, Martine Moreau, Thierry Huby, Giacomo Paonessa, Claudia Santini, Alessandra Luzzago, Charles M Rice, Riccardo Cortese, Alessandra Vitelli, Alfredo Nicosia
• Journal: Journal of virology (J Virol) Vol. 81 Issue 15 Pg. 8063-71 (Aug 2007) ISSN: 0022-538X [Print] United States
• PMID: 17507483 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Lipoproteins, HDL
• SCARB1 protein, human
• Scavenger Receptors, Class B
• Cholesterol

Topics

• Antibodies, Monoclonal (immunology)
• Antibody Affinity
• Cell Line
• Cholesterol (metabolism)
• Hepacivirus (immunology)
• Hepatitis C (immunology, prevention & control)
• Humans
• Lipoproteins, HDL (metabolism)
• Scavenger Receptors, Class B (genetics, immunology)