title: Cellular glycosaminoglycans and low density lipoprotein receptor are involved in hepatitis C virus adsorption.
abstract: The initial binding of Hepatitis C virus (HCV) to the cell membrane is a critical determinant of pathogenesis. Two putative HCV receptors have been identified, CD81 and low-density lipoprotein receptor (LDLr). CD81 interacts in vitro with the HCV E2 envelope glycoprotein, and LDLr interacts with HCV present in human plasma. In order to characterize these potential receptors for HCV, virus from plasma, able to replicate in cell culture, was inoculated on Vero cells or human hepatocarcinoma cells. HCV adsorption was assessed by quantitating cell-associated viral RNA by a real-time RT-PCR method. Anti-LDLr antibody, low and very low density lipoproteins inhibited significantly HCV adsorption, confirming the role of LDLr as HCV receptor. Only one out of the two anti-CD81 antibodies used in this study led to a partial inhibition of HCV binding. This study also highlights a role for glycosaminoglycans (GAGs) in HCV adsorption: treatment of virus with heparin led to 70% inhibition of attachment, as did desulfation of cellular GAGs. Treatment of Vero cells with heparin-lyase significantly inhibited virus attachment but by only 30%. These results demonstrate the complexity of the HCV binding step in which LDLr interacts strongly with HCV, whereas the interaction of HCV with GAGs and particularly with CD81 seem to be more moderate.
authors.affiliation: Laboratoire de Virologie Moléculaire et Structurale EA 2939, Université Joseph Fourier, Faculté de Médecine-Pharmacie de Grenoble, La Tronche, France.
authors.forename: Raphaële
authors.initials: R
authors.lastname: Germi
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Crance
authors.forename: Daniel
authors.initials: D
authors.lastname: Garin
authors.forename: Josette
authors.initials: J
authors.lastname: Guimet
authors.forename: Hugues
authors.initials: H
authors.lastname: Lortat-Jacob
authors.forename: Rob W H
authors.initials: RW
authors.lastname: Ruigrok
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Zarski
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Drouet
mesh_terms: D000327:Adsorption; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001665:Binding Sites; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002522:Chlorocebus aethiops; D006025:Glycosaminoglycans / Q000378:metabolism*; D016174:Hepacivirus / Q000378:metabolism* / Q000472:pathogenicity*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008565:Membrane Proteins; D011973:Receptors, LDL / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism; D060225:Tetraspanin 28; D014709:Vero Cells
chemical_list: D015703:Antigens, CD; C554798:CD81 protein, human; D006025:Glycosaminoglycans; D008565:Membrane Proteins; D011973:Receptors, LDL; D011991:Receptors, Virus; D060225:Tetraspanin 28; C013786:A73025; D006493:Heparin