title: Host cell kinases and the hepatitis C virus life cycle.
abstract: Hepatitis C virus (HCV) infection relies on virus-host interactions with human hepatocytes, a context in which host cell kinases play critical roles in every step of the HCV life cycle. During viral entry, cellular kinases, including EGFR, EphA2 and PKA, regulate the localization of host HCV entry factors and induce receptor complex assembly. Following virion internalization, viral genomes replicate on endoplasmic reticulum-derived membranous webs. The formation of membranous webs depends on interactions between the HCV NS5a protein and PI4KIIIα. The phosphorylation status of NS5a, regulated by PI4KIIIα, CKI and other kinases, also acts as a molecular switch to virion assembly, which takes place on lipid droplets. The formation of lipid droplets is enhanced by HCV activation of IKKα. In view of the multiple crucial steps in the viral life cycle that are mediated by host cell kinases, these enzymes also represent complementary targets for antiviral therapy. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases.
authors.affiliation: Inserm U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France; Université de Strasbourg, 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, Strasbourg, France; Université de Strasbourg, Strasbourg, France.
authors.forename: Joachim
authors.initials: J
authors.lastname: Lupberger
authors.affiliation: Department of Microbiology, School of Biomedical Sciences, Monash University, Victoria, Australia.
authors.forename: Christian
authors.initials: C
authors.lastname: Doerig
authors.affiliation: Inserm U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France; Université de Strasbourg, Strasbourg, France; Institut Hospitalo-Universitaire, Pôle Hépato-digestif, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. Electronic address: thomas.baumert@unistra.fr.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Baumert
mesh_terms: D000818:Animals; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D016174:Hepacivirus / Q000235:genetics* / Q000472:pathogenicity; D006526:Hepatitis C / Q000235:genetics* / Q000821:virology; D022781:Hepatocytes / Q000201:enzymology / Q000821:virology; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D008018:Life Cycle Stages / Q000235:genetics; D015778:Minor Histocompatibility Antigens; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D036104:Receptor, EphA2 / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000235:genetics; D019065:Virus Assembly / Q000235:genetics; D053586:Virus Internalization; D012324:RNA-Dependent RNA Polymerase
chemical_list: D066246:ErbB Receptors; D015778:Minor Histocompatibility Antigens; D017853:Phosphotransferases (Alcohol Group Acceptor); D036104:Receptor, EphA2; D017361:Viral Nonstructural Proteins; C402182:phosphatidylinositol phosphate 4-kinase; C512478:EGFR protein, human; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: Hepatitis C virus; Host cell kinases; Virus–host interactions