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Inhibition of Akt kinase activity suppresses entry and replication of influenza virus

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Title: Inhibition of Akt kinase activity suppresses entry and replication of influenza virus
Authors: Hirata, Noriyuki Browse this author
Suizu, Futoshi Browse this author →KAKEN DB
Matsuda-Lennikov, Mami Browse this author
Edamura, Tatsuma Browse this author
Bala, Jyoti Browse this author
Noguchi, Masayuki Browse this author →KAKEN DB
Keywords: Influenza virus
PI3K-Akt signaling
Akt inhibitor
Issue Date: 18-Jul-2014
Publisher: Elsevier
Journal Title: Biochemical and Biophysical Research Communications
Volume: 450
Issue: 1
Start Page: 891
End Page: 898
Publisher DOI: 10.1016/j.bbrc.2014.06.077
PMID: 24971535
Abstract: The possibility of the pandemic spread of influenza viruses highlights the need for an effective cure for this life-threatening disease. Influenza A virus, belonging to a family of orthomyxoviruses, is a negative-strand RNA virus which encodes 11 viral proteins. A numbers of intracellular signaling pathways in the host cells interact with influenza the viral proteins, which affect various stages of viral infection and replication. In this study, we investigated how inhibition of Akt kinase activity impacts on influenza virus infection by using "Akt-in", a peptide Akt inhibitor. In PR8 influenza-infected A549 cells, Akt interacted with the NS1 (Non structural protein 1), and hence increased phosphorylation of Akt kinase activity and NS1. Treatment of cells with either "TCL1- or TCL1b-based Akt-in" efficiently suppressed Akt kinase activity while decreasing the levels of phosphorylated NSI; this, in turn, inhibited viral replication in a dose- and time-dependent manner. The inhibitory effect on viral replication appears to not be due to inhibition of the production of inflammatory cytokines, including IL-6 and IL-8, in the host cells. Inhibition of Akt kinase activity in the host cells inhibited the efficiency of viral entry, which is associated with decreased levels of phosphorylated glycogen synthase kinase 3, a substrate of Ala. Thus inhibition of Akt kinase activity in host cells may have therapeutic advantages for influenza virus infection by inhibiting viral entry and replication. (C) 2014 The Authors. Published by Elsevier Inc.
Rights: http://creativecommons.org/licenses/by-nc-nd/3.0/deed.ja
Type: article
URI: http://hdl.handle.net/2115/57508
Appears in Collections:遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 野口 昌幸

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