title: High density lipoproteins facilitate hepatitis C virus entry through the scavenger receptor class B type I.
abstract: The scavenger receptor class B type I (SR-BI) has recently been shown to interact with hepatitis C virus (HCV) envelope glycoprotein E2, suggesting that it might be involved at some step of HCV entry into host cells. However, due to the absence of a cell culture system to efficiently amplify HCV, it is not clear how SR-BI contributes to HCV entry. Here, we sought to determine how high density lipoproteins (HDLs), the natural ligand of SR-BI, affect HCV entry. By using the recently described infectious HCV pseudotyped particles (HCVpps) that display functional E1E2 glycoprotein complexes, we showed that HDLs are able to markedly enhance HCVpp entry. We did not find any evidence of HDL association with HCVpps, suggesting that HCVpps do not enter into target cells using HDL as a carrier to bind to its receptor. Interestingly, lipid-free apoA-I and apoA-II, the major HDL apolipoproteins, were unable to enhance HCVpp infectivity. In addition, drugs inhibiting HDL cholesteryl transfer (block lipid transport (BLT)-2 and BLT-4) reduced HDL enhancement of HCVpp entry, suggesting a role for lipid transfer in facilitating HCVpp entry. Importantly, silencing of SR-BI expression in target cells by RNA interference markedly reduced HDL-mediated enhancement of HCVpp entry. Finally, enhancement of HCVpp entry was also suppressed when the SR-BI binding region on HCV glycoprotein E2 was deleted. Altogether, these data indicate that HDL-mediated enhancement of HCVpp entry involves a complex interplay between SR-BI, HDL, and HCV envelope glycoproteins, and they highlight the active role of HDLs in HCV entry.
authors.affiliation: CNRS-UPR2511, Institut de Biologie de Lille and Institut Pasteur de Lille, Lille 59021, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Voisset
authors.forename: Nathalie
authors.initials: N
authors.lastname: Callens
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Blanchard
authors.forename: Anne
authors.initials: A
authors.lastname: Op De Beeck
authors.forename: Jean
authors.initials: J
authors.lastname: Dubuisson
authors.forename: Ngoc
authors.initials: N
authors.lastname: Vu-Dac
mesh_terms: D018955:CD36 Antigens; D002460:Cell Line; D002499:Centrifugation, Density Gradient; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D020868:Gene Silencing; D006023:Glycoproteins / Q000737:chemistry; D016174:Hepacivirus / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008024:Ligands; D008055:Lipids / Q000737:chemistry; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D013395:Sucrose / Q000494:pharmacology; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D018955:CD36 Antigens; D006023:Glycoproteins; D008024:Ligands; D008055:Lipids; D008075:Lipoproteins, HDL; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D014759:Viral Envelope Proteins; D013395:Sucrose