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

• Hirata, Noriyuki

• Suizu, Futoshi

• Matsuda-Lennikov, Mami

• Edamura, Tatsuma

• Bala, Jyoti

• Noguchi, Masayuki

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.

Journal

• Biochemical and Biophysical Research Communications

  Biochemical and Biophysical Research Communications 450 (1), 891-898, 2014-07-18

  Elsevier

Keywords

• Influenza virus
• PI3K-Akt signaling
• Akt inhibitor

Details

• CRID: 1050564288970428160
• NII Article ID: 120005517702
• DOI: 10.1016/j.bbrc.2014.06.077
• HANDLE: 2115/57508
• ISSN: 0006291X
• Web Site: https://api.elsevier.com/content/article/PII:S0006291X14011516?httpAccept=text/plain
• Web Site: https://api.elsevier.com/content/article/PII:S0006291X14011516?httpAccept=text/xml
• Text Lang: en
• Article Type: journal article
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