Skip to Main content Skip to Navigation
Journal articles

High density lipoprotein inhibits hepatitis C virus-neutralizing antibodies by stimulating cell entry via activation of the scavenger receptor BI.

Abstract : Hepatitis C virus (HCV) exploits serum-dependent mechanisms that inhibit neutralizing antibodies. Here we demonstrate that high density lipoprotein (HDL) is a key serum factor that attenuates neutralization by monoclonal and HCV patient-derived polyclonal antibodies of infectious pseudo-particles (HCVpp) harboring authentic E1E2 glycoproteins and cell culture-grown genuine HCV (HCVcc). Over 10-fold higher antibody concentrations are required to neutralize either HCV-enveloped particles in the presence of HDL or human serum, and less than 3-5-fold reduction of infectious titers are obtained at saturating antibody concentrations, in contrast to complete inhibition in serum-free conditions. We show that HDL interaction with the scavenger receptor BI (SR-BI), a proposed cell entry co-factor of HCV and a receptor mediating lipid transfer with HDL, strongly reduces neutralization of HCVpp and HCVcc. We found that HDL activation of target cells strongly stimulates cell entry of viral particles by accelerating their endocytosis, thereby suppressing a 1-h time lag during which cell-bound virions are not internalized and can be targeted by antibodies. Compounds that inhibit lipid transfer functions of SR-BI fully restore neutralization by antibodies in human serum. We demonstrate that this functional HDL/SR-BI interaction only interferes with antibodies blocking HCV-E2 binding to CD81, a major HCV receptor, reflecting its prominent role during the cell entry process. Moreover, we identify monoclonal antibodies targeted to epitopes in the E1E2 complex that are not inhibited by HDL. Consistently, we show that antibodies targeted to HCV-E1 efficiently neutralize HCVpp and HCVcc in the presence of human serum.
Document type :
Journal articles
Complete list of metadatas

Cited literature [57 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-00133952
Contributor : François-Loïc Cosset <>
Submitted on : Wednesday, February 28, 2007 - 11:12:32 AM
Last modification on : Thursday, November 21, 2019 - 2:24:04 AM
Long-term archiving on: : Friday, November 25, 2016 - 2:59:58 PM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Collections

Citation

Marlène Dreux, Thomas Pietschmann, Christelle Granier, Cécile Voisset, Sylvie Ricard-Blum, et al.. High density lipoprotein inhibits hepatitis C virus-neutralizing antibodies by stimulating cell entry via activation of the scavenger receptor BI.. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2006, 281 (27), pp.18285-95. ⟨10.1074/jbc.M602706200⟩. ⟨inserm-00133952⟩

Share

Metrics

Record views

324