title: The exchangeable apolipoprotein ApoC-I promotes membrane fusion of hepatitis C virus.
abstract: Cell entry of hepatitis C virus (HCV) is strikingly linked to lipoproteins and their receptors. Particularly, high density lipoprotein (HDL) enhances infectivity of HCV by involving the lipid-transfer function of the scavenger receptor BI, a receptor for both HDL and HCV. Here, we demonstrate that apoC-I, an exchangeable apolipoprotein that predominantly resides in HDL, specifically enhances HCVcc and HCVpp infectivity and increases the fusion rates between viral and target membranes via a direct interaction with the HCV surface. We identify the hypervariable region 1, located at the N terminus of the HCV E2 glycoprotein, as an essential viral component that modulates apoC-I-mediated enhancement of HCV fusion properties. The affinity of apoC-I for the HCV membrane may predispose it for fusion with a target membrane via alterations of its outer phospholipid layer. Conversely, we found that excess apoC-I provided as lipoprotein-free protein induces the disruption of the HCV membrane and subsequent loss of infectivity. Furthermore, our data indicate that HDL neither interacts nor spontaneously exchanges apoC-I with HCV virions. Because apoC-I is not present in serum as a lipoprotein-free form, our results suggest that HDL-embedded apoC-I could be released from the lipoprotein particle through a fine-tuned mechanism regulated via a triple interplay between hypervariable region 1, HDL, and scavenger receptor BI, resulting in optimal apoC-I recruitment on the viral membrane. These results provide the first description of a host serum factor helping the fusion process of an enveloped virus.
authors.affiliation: Université de Lyon, (UCB-Lyon1), IFR128, INSERM, U758, and Ecole Normale Supérieure de Lyon, Lyon, F-69007, France.
authors.forename: Marlène
authors.initials: M
authors.lastname: Dreux
authors.forename: Bertrand
authors.initials: B
authors.lastname: Boson
authors.forename: Sylvie
authors.initials: S
authors.lastname: Ricard-Blum
authors.forename: Jennifer
authors.initials: J
authors.lastname: Molle
authors.forename: Dimitri
authors.initials: D
authors.lastname: Lavillette
authors.forename: Birke
authors.initials: B
authors.lastname: Bartosch
authors.forename: Eve-Isabelle
authors.initials: EI
authors.lastname: Pécheur
authors.forename: Francois-Loïc
authors.initials: FL
authors.lastname: Cosset
mesh_terms: D053302:Apolipoprotein C-I / Q000378:metabolism*; D045744:Cell Line, Tumor; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism; D053586:Virus Internalization
chemical_list: C505803:APOC1 protein, human; D053302:Apolipoprotein C-I; C400562:HVR1 protein, Hepatitis C virus; D008075:Lipoproteins, HDL; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D014764:Viral Proteins