Autophagy is involved in the replication of H9N2 influenza virus via the regulation of oxidative stress in alveolar epithelial cells.

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  • Additional Information
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 101231645 Publication Model: Electronic Cited Medium: Internet ISSN: 1743-422X (Electronic) Linking ISSN: 1743422X NLM ISO Abbreviation: Virol J Subsets: MEDLINE
    • Publication Information:
      Original Publication: [London] : BioMed Central, 2004-
    • Subject Terms:
      Gene Expression Regulation* ; Virus Replication*; Alveolar Epithelial Cells/*virology ; Autophagy/*genetics ; Influenza A Virus, H9N2 Subtype/*physiology ; Orthomyxoviridae Infections/*veterinary ; Oxidative Stress/*genetics; A549 Cells ; Animals ; Humans ; Influenza A Virus, H9N2 Subtype/pathogenicity ; Signal Transduction ; Swine
    • Abstract:
      Background: Oxidative stress is an important pathogenic factor in influenza A virus infection. It has been found that reactive oxygen species induced by the H9N2 influenza virus is associated with viral replication. However, the mechanisms involved remain to be elucidated.
      Methods: In this study, the role of autophagy was investigated in H9N2 influenza virus-induced oxidative stress and viral replication in A549 cells. Autophagy induced by H9N2 was inhibited by an autophagy inhibitor or RNA interference, the autophagy level, viral replication and the presence of oxidative stress were detected by western blot, TCID50 assay, and Real-time PCR. Then autophagy and oxidative stress were regulated, and viral replication was determined. At last, the Akt/TSC2/mTOR signaling pathways was detected by western blot.
      Results: Autophagy was induced by the H9N2 influenza virus and the inhibition of autophagy reduced the viral titer and the expression of nucleoprotein and matrix protein. The blockage of autophagy suppressed the H9N2 virus-induced increase in the presence of oxidative stress, as evidenced by decreased reactive oxygen species production and malonaldehyde generation, and increased superoxide dismutase 1 levels. The changes in the viral titer and NP mRNA level caused by the antioxidant, N-acetyl-cysteine (NAC), and the oxidizing agent, H 2 O 2 , confirmed the involvement of oxidative stress in the control of viral replication. NAC plus transfection with Atg5 siRNA significantly reduced the viral titer and oxidative stress compared with NAC treatment alone, which confirmed that autophagy was involved in the replication of H9N2 influenza virus by regulating oxidative stress. Our data also revealed that autophagy was induced by the H9N2 influenza virus through the Akt/TSC2/mTOR pathway. The activation of Akt or the inhibition of TSC2 suppressed the H9N2 virus-induced increase in the level of LC3-II, restored the decrease in the expression of phospho-pAkt, phospho-mTOR and phospho-pS6 caused by H9N2 infection, suppressed the H9N2-induced increase in the presence of oxidative stress, and resulted in a decrease in the viral titer.
      Conclusion: Autophagy is involved in H9N2 virus replication by regulating oxidative stress via the Akt/TSC2/mTOR signaling pathway. Thus, autophagy maybe a target which may be used to improve antiviral therapeutics.
    • References:
      J Virol. 2019 Feb 5;93(4):. (PMID: 30541828)
      J Neuroinflammation. 2016 Jun 10;13(1):142. (PMID: 27282914)
      Cell. 2014 Dec 4;159(6):1263-76. (PMID: 25480292)
      Cell Microbiol. 2015 Jan;17(1):131-45. (PMID: 25154738)
      J Gen Virol. 2015 Oct;96(10):2939-2950. (PMID: 26233716)
      Int J Biochem Cell Biol. 2016 Mar;72:100-108. (PMID: 26794463)
      Biochimie. 2008 Feb;90(2):313-23. (PMID: 17928127)
      Annu Rev Pathol. 2008;3:499-522. (PMID: 18039138)
      Cell. 2003 Nov 26;115(5):577-90. (PMID: 14651849)
      Biochem Biophys Res Commun. 2018 Apr 15;498(4):960-966. (PMID: 29548827)
      Autophagy. 2008 Oct;4(7):851-65. (PMID: 18670193)
      Am J Physiol Lung Cell Mol Physiol. 2010 Dec;299(6):L843-51. (PMID: 20935232)
      Anim Health Res Rev. 2010 Jun;11(1):3-18. (PMID: 20591210)
      Cell Res. 2014 Jan;24(1):42-57. (PMID: 24343578)
      EMBO J. 2012 Nov 14;31(22):4304-17. (PMID: 23064152)
      Viral Immunol. 1999;12(3):175-96. (PMID: 10532647)
      Annu Rev Cell Dev Biol. 2011;27:107-32. (PMID: 21801009)
      Cell Physiol Biochem. 2015;36(3):1223-36. (PMID: 26138883)
      Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2011 Jun;25(3):205-7. (PMID: 21977593)
      Autophagy. 2006 Jul-Sep;2(3):200-8. (PMID: 16874114)
      Biochem Biophys Res Commun. 2004 Jan 9;313(2):453-8. (PMID: 14684184)
      Cell Host Microbe. 2009 Oct 22;6(4):367-80. (PMID: 19837376)
      Autophagy. 2009 Apr;5(3):321-8. (PMID: 19066474)
      Genes Dev. 2007 Nov 15;21(22):2861-73. (PMID: 18006683)
      Ann Clin Lab Sci. 2019 Jan;49(1):3-8. (PMID: 30814071)
      Int Immunopharmacol. 2017 Nov;52:24-33. (PMID: 28858723)
      J Genet Genomics. 2011 Nov 20;38(11):533-7. (PMID: 22133684)
      Physiol Rev. 2007 Jan;87(1):245-313. (PMID: 17237347)
      Calcif Tissue Int. 2019 Jul;105(1):89-96. (PMID: 30809689)
      PLoS One. 2012;7(8):e42706. (PMID: 22900043)
      J Virol. 2013 Dec;87(24):13107-14. (PMID: 24027311)
      Autophagy. 2007 Nov-Dec;3(6):542-5. (PMID: 17611390)
      PLoS Pathog. 2011 Feb 03;7(2):e1001271. (PMID: 21304882)
      Biochem Biophys Res Commun. 2014 Jul 18;450(1):711-6. (PMID: 24946209)
      Nat Rev Mol Cell Biol. 2005 Jun;6(6):505-10. (PMID: 15928714)
      Emerg Infect Dis. 2007 May;13(5):708-12. (PMID: 17553248)
      Autophagy. 2013 Feb 1;9(2):175-95. (PMID: 23169238)
      Cell Mol Immunol. 2010 Jul;7(4):263-70. (PMID: 20473322)
      Sci Signal. 2012 Feb 21;5(212):ra16. (PMID: 22355189)
      J Virol. 2013 Jan;87(2):1049-60. (PMID: 23135712)
      Genes Dev. 2003 Aug 1;17(15):1829-34. (PMID: 12869586)
      Free Radic Biol Med. 2003 Apr 1;34(7):928-36. (PMID: 12654482)
      Int Immunopharmacol. 2014 Sep;22(1):1-8. (PMID: 24968347)
      Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2008 Jun;22(3):180-2. (PMID: 19031696)
      Trends Immunol. 2005 Oct;26(10):523-8. (PMID: 16099218)
      J Virol. 1984 Aug;51(2):497-504. (PMID: 6431119)
      Cell Mol Neurobiol. 2016 Aug;36(6):915-925. (PMID: 26440805)
      PLoS One. 2014 Oct 14;9(10):e109023. (PMID: 25313647)
      Am J Physiol Lung Cell Mol Physiol. 2015 Feb 1;308(3):L270-86. (PMID: 25361566)
      Curr Clin Pharmacol. 2014 May;9(2):93-115. (PMID: 23441838)
      Biomed Pharmacother. 2017 May;89:660-672. (PMID: 28262619)
      J Virol. 1996 Dec;70(12):8391-401. (PMID: 8970960)
      J Virol. 2007 Mar;81(6):2736-44. (PMID: 17182684)
      Nature. 2018 Jun;558(7708):136-140. (PMID: 29849149)
      J Virol. 2011 Jul;85(13):6453-63. (PMID: 21525345)
      Nat Rev Mol Cell Biol. 2007 Nov;8(11):931-7. (PMID: 17712358)
    • Contributed Indexing:
      Keywords: Akt/mTOR; Autophagy; H9N2 influenza virus; Oxidative stress; Virus replication
    • Publication Date:
      Date Created: 20210119 Date Completed: 20210902 Latest Revision: 20210902
    • Publication Date:
      20231215
    • Accession Number:
      PMC7814439
    • Accession Number:
      10.1186/s12985-020-01484-x
    • Accession Number:
      33461581