title: High-throughput approaches to unravel hepatitis C virus-host interactions.
abstract: Hepatitis C virus (HCV) remains a major global health burden, with more than 130 million individuals chronically infected and at risk for the development of hepatocellular carcinoma (HCC). The recent clinical licensing of direct-acting antivirals enables viral cure. However, limited access to therapy and treatment failure in patient subgroups warrants a continuing effort to develop complementary antiviral strategies. Furthermore, once fibrosis is established, curing HCV infection does not eliminate the risk for HCC. High-throughput approaches and screens have enabled the investigation of virus-host interactions on a genome-wide scale. Gain- and loss-of-function screens have identified essential host-dependency factors in the HCV viral life cycle, such as host cell entry factors or regulatory factors for viral replication and assembly. Network analyses of systems-scale data sets provided a comprehensive view of the cellular state following HCV infection, thus improving our understanding of the virus-induced responses of the target cell. Interactome, metabolomics and gene expression studies identified dysregulated cellular processes potentially contributing to HCV pathogenesis and HCC. Drug screens using chemical libraries led to the discovery of novel antivirals. Here, we review the contribution of high-throughput approaches for the investigation of virus-host interactions, viral pathogenesis and drug discovery.
authors.affiliation: Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 67000 Strasbourg, France; Université de Strasbourg, 67000 Strasbourg, France.
authors.forename: Che C
authors.initials: CC
authors.lastname: Colpitts
authors.affiliation: Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 67000 Strasbourg, France; Université de Strasbourg, 67000 Strasbourg, France.
authors.forename: Hussein
authors.initials: H
authors.lastname: El-Saghire
authors.affiliation: Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital, Harvard Medical School, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pochet
authors.affiliation: Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 67000 Strasbourg, France; Université de Strasbourg, 67000 Strasbourg, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Schuster
authors.affiliation: Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 67000 Strasbourg, France; Université de Strasbourg, 67000 Strasbourg, France; Institut Hospitalo-Universitaire, PôleHépato-digestif, HôpitauxUniversitaires de Strasbourg, 67000 Strasbourg, France. Electronic address: thomas.baumert@unistra.fr.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Baumert
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000627:therapeutic use; D057167:Claudins / Q000235:genetics / Q000378:metabolism; D036383:Ephrin-A2 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D006526:Hepatitis C / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000821:virology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D057166:High-Throughput Screening Assays; D054884:Host-Pathogen Interactions; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D062793:Occludin / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D036104:Receptor, EphA2; D015398:Signal Transduction; D049490:Systems Biology / Q000379:methods*; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D057167:Claudins; C000623258:EPHA2 protein, human; D036383:Ephrin-A2; C568985:OCLN protein, human; D062793:Occludin; D014764:Viral Proteins; D036104:Receptor, EphA2; C486061:NUAK2 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: HCV pathogenesis; Hepatitis C virus; Systems biology; Virus-host interactions