Hepatitis C Virus RNA-Dependent RNA Polymerase Interacts with the Akt/PKB Kinase and Induces Its Subcellular Relocalization
Year: 2016
Type: article
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.
DOI: 10.1128/aac.03019-15
Institutions: University of Castilla-La Mancha, Universitat Autònoma de Barcelona, Consejo Superior de Investigaciones Científicas, Vall d'Hebron Institut de Recerca, Vall d'Hebron Hospital Universitari, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid
Language: English
Topic: Hepatitis C virus research
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2396721130