title: Hepatitis C Virus RNA-Dependent RNA Polymerase Interacts with the Akt/PKB Kinase and Induces Its Subcellular Relocalization.
abstract: Hepatitis C virus (HCV) interacts with cellular components and modulates their activities for its own benefit. These interactions have been postulated as a target for antiviral treatment, and some candidate molecules are currently in clinical trials. The multifunctional cellular kinase Akt/protein kinase B (PKB) must be activated to increase the efficacy of HCV entry but is rapidly inactivated as the viral replication cycle progresses. Viral components have been postulated to be responsible for Akt/PKB inactivation, but the underlying mechanism remained elusive. In this study, we show that HCV polymerase NS5B interacts with Akt/PKB. In the presence of transiently expressed NS5B or in replicon- or virus-infected cells, NS5B changes the cellular localization of Akt/PKB from the cytoplasm to the perinuclear region. Sequestration of Akt/PKB by NS5B could explain its exclusion from its participation in early Akt/PKB inactivation. The NS5B-Akt/PKB interaction represents a new regulatory step in the HCV infection cycle, opening possibilities for new therapeutic options.
authors.affiliation: Laboratorio de Virología Molecular, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla-La Mancha, Albacete, Spain.
authors.forename: María Llanos
authors.initials: ML
authors.lastname: Valero
authors.affiliation: Laboratorio de Virología Molecular, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla-La Mancha, Albacete, Spain Facultad de Medicina, Universidad de Castilla-La Mancha, Albacete, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: Sabariegos
authors.affiliation: Laboratorio de Oncología Molecular, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla-La Mancha, Albacete, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Cimas
authors.affiliation: Centro de Biología Molecular "Severo Ochoa," CSIC-UAM, Cantoblanco, Madrid, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain Liver Unit, Internal Medicine, Laboratory of Malalties Hepàtiques, Vall d'Hebron Institut de Recerca-Hospital Universitari Vall d'Hebron, (VHIR-HUVH), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Perales
authors.affiliation: Centro de Biología Molecular "Severo Ochoa," CSIC-UAM, Cantoblanco, Madrid, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain Unidad de Biomedicina UCLM-CSIC, Albacete, Spain.
authors.forename: Esteban
authors.initials: E
authors.lastname: Domingo
authors.affiliation: Laboratorio de Oncología Molecular, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla-La Mancha, Albacete, Spain Unidad de Biomedicina UCLM-CSIC, Albacete, Spain Parque Científico y Tecnológico de Albacete (PCyTA), Albacete, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Sánchez-Prieto
authors.affiliation: Laboratorio de Virología Molecular, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla-La Mancha, Albacete, Spain Facultad de Farmacia, Universidad de Castilla-La Mancha, Albacete, Spain Unidad de Biomedicina UCLM-CSIC, Albacete, Spain Antonio.Mas@uclm.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: Mas
mesh_terms: D045744:Cell Line, Tumor; D016174:Hepacivirus / Q000201:enzymology*; D006526:Hepatitis C / Q000473:pathology* / Q000821:virology; D006801:Humans; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012324:RNA-Dependent RNA Polymerase / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology
chemical_list: D017361:Viral Nonstructural Proteins; D051057:Proto-Oncogene Proteins c-akt; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase