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Hepatitis C Virus RNA-Dependent RNA Polymerase Interacts with the Akt/PKB Kinase and Induces Its Subcellular Relocalization

AutorValero, María Llanos; Sabariegos Jareño, Mª del Rosario; Cimas Francisco J.; Perales, Celia ; Domingo, Esteban ; Mas, Antonio
Fecha de publicación28-mar-2016
EditorAmerican Society for Microbiology
CitaciónAntimicrobial Agents and Chemotherapy 60: 3540- 3550 (2016)
ResumenHepatitis 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.
URIhttp://hdl.handle.net/10261/151537
DOI10.1128/AAC.03019-15
Identificadoresdoi: 10.1128/AAC.03019-15
issn: 1098-6596
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