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

• DOI: 10.1016/j.bbrc.2014.06.077
• Publication Date: 2014-06-24T15:02:25Z
• Authors: Noriyuki Hirata; Futoshi Suizu; Mami Matsuda-Lenn...; Tatsuma Edamura; Jyoti Bala; Masayuki Noguchi
• Keywords: 0301 basic medicine; 490; Biophysics; Cell Biology; Virus Internalization; Virus Replication; Biochemistry; Madin Darby Canine Kidney Cells; 3. Good health; Enzyme Activation; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; PI3K-Akt signaling; Dogs; Influenza A virus; Animals; Humans; PI3K–Akt signaling; Akt inhibitor; Influenza virus; Molecular Biology; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt

The possibility of the pandemic spread influenza viruses highlights need for an effective cure this life-threatening disease. Influenza A virus, belonging to a family orthomyxoviruses, is negative-strand RNA virus which encodes 11 viral proteins. numbers intracellular signaling pathways in host cells interact with proteins, affect various stages infection and replication. In study, we investigated how inhibition Akt kinase activity impacts on by using "Akt-in", peptide inhibitor. PR8 influenza-infected A549 cells, interacted NS1 (Non structural protein 1), hence increased phosphorylation NS1. Treatment either "TCL1- or TCL1b-based Akt-in" efficiently suppressed while decreasing levels phosphorylated NS1; this, turn, inhibited replication dose- time-dependent manner. inhibitory effect appears not be due production inflammatory cytokines, including IL-6 IL-8, cells. Inhibition efficiency entry, associated decreased glycogen synthase 3, substrate Akt. Thus may have therapeutic advantages inhibiting entry