title: Lipids: a key for hepatitis C virus entry and a potential target for antiviral strategies.
abstract: Viruses have evolved to complex relationship with their host cells. Many viruses modulate the lipid composition, lipid synthesis and signaling of their host cell. Lipids are also an essential part of the life cycle of the hepatitis C virus (HCV). HCV is a major human pathogen, persistently infecting 170 million people worldwide, with no currently effective treatment available for all patients. HCV appears to make use of the host lipid metabolism and one common feature of chronic hepatitis C is the steatosis, characterized by excessive accumulation of triglycerides and lipid content in the liver. Thus, HCV lifecycle appears to be closely connected to host cell lipid metabolism, from cell entry, through viral RNA replication to viral particle production and formation/assembly. HCV particles have a unique lipid composition, certainly distinct from other viruses. In the blood of chronically-infected patients, viral particles are bound to serum lipoproteins and are thus called lipo-viro-particles. The density of these circulating viral particles is heterogeneous. Specific infectivity and fusion of low density particles are greater than those of high density particles. Lipids and association to lipoproteins therefore play a key role in HCV life cycle. The purpose of this review is to make a state of the art on recent findings on the contribution of lipids in cell entry and membrane fusion of HCV. The influence of lipids as chemically-defined entities will be analyzed, as well as the role played by cholesterol transporters and lipoprotein receptors in HCV entry and fusion. Since viral entry would constitute a key target for antiviral strategies, inhibitor molecules interacting with viral and/or cellular membranes or interfering with the function of lipid metabolism regulators of HCV entry could offer strong antiviral potential. This will be lastly discussed in this review.
authors.affiliation: UMR INSERM U1052/CNRS 5286, Centre de Recherche en Cancérologie de Lyon, Université de Lyon, Lyon cedex, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Blaising
authors.forename: Eve-Isabelle
authors.initials: EI
authors.lastname: Pécheur
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism; D006526:Hepatitis C / Q000188:drug therapy / Q000378:metabolism / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry*; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000821:virology; D008561:Membrane Fusion; D058990:Molecular Targeted Therapy; D014771:Virion / Q000737:chemistry / Q000378:metabolism / Q000472:pathogenicity
chemical_list: D000998:Antiviral Agents; D008055:Lipids; D008074:Lipoproteins