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Influenza A virus-induced apoptosis and virus propagation

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Abstract

Influenza A viruses (IAVs) are respiratory pathogens that cause severe morbidity and mortality worldwide. They affect cellular processes such as proliferation, protein synthesis, autophagy, and apoptosis. Although apoptosis is considered an innate cellular response to invading infectious pathogens, IAVs have evolved to encode viral proteins that modulate host cellular apoptosis in ways that support efficient viral replication and propagation. An understanding of the modulation of host responses is essential to the development of novel therapeutics for the treatment of IAV infections. In this review, we discuss the IAV lifecycle, biology, and strategies employed by the virus to modulate apoptosis to enhance viral survival and establish an infection.

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(Adapted from Viral control of mitochondrial apoptosis [67])

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References

  1. 1.

    WHO (2013) Pandemic influenza preparedness and response: a WHO guidance document. World Health Organization, WHO

  2. 2.

    Sun J, Madan R, Karp CL, Braciale TJ (2009) Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10. Nat Med 15:277–284

  3. 3.

    Taubenberger JK, Morens DM (2008) The pathology of influenza virus infections. Annu Rev Pathol 3:499–522

  4. 4.

    Plans-Rubio P (2007) Prevention and control of influenza in persons with chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2:41–53

  5. 5.

    Taubenberger JK, Kash JC (2010) Influenza virus evolution, host adaptation, and pandemic formation. Cell Host Microbe 7:440–451

  6. 6.

    Muller KH, Kakkola L, Nagaraj AS, Cheltsov AV, Anastasina M, Kainov DE (2012) Emerging cellular targets for influenza antiviral agents. Trends Pharmacol Sci 33:89–99

  7. 7.

    Nelson MI, Holmes EC (2007) The evolution of epidemic influenza. Nat Rev Genet 8:196–205

  8. 8.

    Gao H, Sun H, Hu J et al (2015) Twenty amino acids at the C-terminus of PA-X are associated with increased influenza A virus replication and pathogenicity. J Gen Virol 96:2036–2049

  9. 9.

    Bouvier NM, Palese P (2008) The biology of influenza viruses. Vaccine 26(Suppl 4):D49–D53

  10. 10.

    Chao DL, Bloom JD, Kochin BF, Antia R, Longini IM Jr (2012) The global spread of drug-resistant influenza. J R Soc Interface 9:648–656

  11. 11.

    Shaw ML, Stone KL, Colangelo CM, Gulcicek EE, Palese P (2008) Cellular proteins in influenza virus particles. PLoS Pathog 4:e1000085

  12. 12.

    Muramoto Y, Noda T, Kawakami E, Akkina R, Kawaoka Y (2013) Identification of novel influenza A virus proteins translated from PA mRNA. J Virol 87:2455–2462

  13. 13.

    Huang TS, Palese P, Krystal M (1990) Determination of influenza virus proteins required for genome replication. J Virol 64:5669–5673

  14. 14.

    Hale BG, Albrecht RA, Garcia-Sastre A (2010) Innate immune evasion strategies of influenza viruses. Future Microbiol 5:23–41

  15. 15.

    Skehel JJ, Schild GC (1971) The polypeptide composition of influenza A viruses. Virology 44:396–408

  16. 16.

    Compans RW, Klenk HD, Caliguiri LA, Choppin PW (1970) Influenza virus proteins. I. Analysis of polypeptides of the virion and identification of spike glycoproteins. Virology 42:880–889

  17. 17.

    O’Neill RE, Talon J, Palese P (1998) The influenza virus NEP (NS2 protein) mediates the nuclear export of viral ribonucleoproteins. EMBO J 17:288–296

  18. 18.

    Bui M, Wills EG, Helenius A, Whittaker GR (2000) Role of the influenza virus M1 protein in nuclear export of viral ribonucleoproteins. J Virol 74:1781–1786

  19. 19.

    Hale BG, Randall RE, Ortin J, Jackson D (2008) The multifunctional NS1 protein of influenza A viruses. J Gen Virol 89:2359–2376

  20. 20.

    Samji T (2009) Influenza A: understanding the viral life cycle. Yale J Biol Med 82:153–159

  21. 21.

    Skehel JJ, Wiley DC (2000) Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annu Rev Biochem 69:531–569

  22. 22.

    Pinto LH, Lamb RA (2006) The M2 proton channels of influenza A and B viruses. J Biol Chem 281:8997–9000

  23. 23.

    Gabriel G, Klingel K, Otte A et al (2011) Differential use of importin-alpha isoforms governs cell tropism and host adaptation of influenza virus. Nat Commun 2:156

  24. 24.

    Wu WW, Pante N (2009) The directionality of the nuclear transport of the influenza A genome is driven by selective exposure of nuclear localization sequences on nucleoprotein. Virol J 6:68

  25. 25.

    Dias A, Bouvier D, Crepin T et al (2009) The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit. Nature 458:914–918

  26. 26.

    Guilligay D, Tarendeau F, Resa-Infante P et al (2008) The structural basis for cap binding by influenza virus polymerase subunit PB2. Nat Struct Mol Biol 15:500–506

  27. 27.

    Chutiwitoonchai N, Mano T, Kakisaka M et al (2017) Inhibition of CRM1-mediated nuclear export of influenza A nucleoprotein and nuclear export protein as a novel target for antiviral drug development. Virology 507:32–39

  28. 28.

    Elton D, Simpson-Holley M, Archer K et al (2001) Interaction of the influenza virus nucleoprotein with the cellular CRM1-mediated nuclear export pathway. J Virol 75:408–419

  29. 29.

    Kash JC, Cunningham DM, Smit MW et al (2002) Selective translation of eukaryotic mRNAs: functional molecular analysis of GRSF-1, a positive regulator of influenza virus protein synthesis. J Virol 76:10417–10426

  30. 30.

    Garfinkel MS, Katze MG (1992) Translational control by influenza virus. Selective and cap-dependent translation of viral mRNAs in infected cells. J Biol Chem 267:9383–9390

  31. 31.

    Wise HM, Hutchinson EC, Jagger BW et al (2012) Identification of a novel splice variant form of the influenza A virus M2 ion channel with an antigenically distinct ectodomain. PLoS Pathog 8:e1002998

  32. 32.

    Fujii Y, Goto H, Watanabe T, Yoshida T, Kawaoka Y (2003) Selective incorporation of influenza virus RNA segments into virions. Proc Natl Acad Sci USA 100:2002–2007

  33. 33.

    Bancroft CT, Parslow TG (2002) Evidence for segment-nonspecific packaging of the influenza a virus genome. J Virol 76:7133–7139

  34. 34.

    Amorim MJ, Bruce EA, Read EK et al (2011) A Rab11- and microtubule-dependent mechanism for cytoplasmic transport of influenza A virus viral RNA. J Virol 85:4143–4156

  35. 35.

    Konig R, Stertz S, Zhou Y et al (2010) Human host factors required for influenza virus replication. Nature 463:813–817

  36. 36.

    Nayak DP, Hui EK, Barman S (2004) Assembly and budding of influenza virus. Virus Res 106:147–165

  37. 37.

    Chen BJ, Lamb RA (2008) Mechanisms for enveloped virus budding: can some viruses do without an ESCRT? Virology 372:221–232

  38. 38.

    Rossman JS, Lamb RA (2011) Influenza virus assembly and budding. Virology 411:229–236

  39. 39.

    Hui EK, Nayak DP (2002) Role of G protein and protein kinase signalling in influenza virus budding in MDCK cells. J Gen Virol 83:3055–3066

  40. 40.

    Christiaansen A, Varga SM, Spencer JV (2015) Viral manipulation of the host immune response. Curr Opin Immunol 36:54–60

  41. 41.

    Ampomah PB, Moraes LA, Lukman HM, Lim LHK (2017) Formyl peptide receptor 2 is regulated by RNA mimics and viruses through an IFN-beta-STAT3-dependent pathway. FASEB J 32:1468

  42. 42.

    Arora S, Lim W, Bist P et al (2016) Influenza A virus enhances its propagation through the modulation of Annexin-A1 dependent endosomal trafficking and apoptosis. Cell Death Differ 23:1243–1256

  43. 43.

    Wilson EB, Brooks DG (2011) The role of IL-10 in regulating immunity to persistent viral infections. Curr Top Microbiol Immunol 350:39–65

  44. 44.

    Ehrhardt C, Wolff T, Pleschka S et al (2007) Influenza A virus NS1 protein activates the PI3 K/Akt pathway to mediate antiapoptotic signaling responses. J Virol 81:3058–3067

  45. 45.

    Zhirnov OP, Konakova TE, Wolff T, Klenk HD (2002) NS1 protein of influenza A virus down-regulates apoptosis. J Virol 76:1617–1625

  46. 46.

    Tran AT, Cortens JP, Du Q, Wilkins JA, Coombs KM (2013) Influenza virus induces apoptosis via BAD-mediated mitochondrial dysregulation. J Virol 87:1049–1060

  47. 47.

    Tripathi S, Batra J, Cao W et al (2013) Influenza A virus nucleoprotein induces apoptosis in human airway epithelial cells: implications of a novel interaction between nucleoprotein and host protein Clusterin. Cell Death Dis 4:e562

  48. 48.

    Pauli EK, Schmolke M, Wolff T et al (2008) Influenza A virus inhibits type I IFN signaling via NF-??B-dependent induction of SOCS-3 expression. PLoS Pathog 4:1–15

  49. 49.

    Pothlichet J, Chignard M, Si-Tahar M (2008) Cutting edge: innate immune response triggered by influenza A virus is negatively regulated by SOCS1 and SOCS3 through a RIG-I/IFNAR1-dependent pathway. J Immunol 180:2034–2038

  50. 50.

    Feizi N, Mehrbod P, Romani B et al (2017) Autophagy induction regulates influenza virus replication in a time-dependent manner. J Med Microbiol 66:536–541

  51. 51.

    Liu G, Zhong M, Guo C et al (2016) Autophagy is involved in regulating influenza A virus RNA and protein synthesis associated with both modulation of Hsp90 induction and mTOR/p70S6 K signaling pathway. Int J Biochem Cell Biol 72:100–108

  52. 52.

    Dougan SK, Ashour J, Karssemeijer RA et al (2013) Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus. Nature 503:406–409

  53. 53.

    Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516

  54. 54.

    Saraste A, Pulkki K (2000) Morphologic and biochemical hallmarks of apoptosis. Cardiovasc Res 45:528–537

  55. 55.

    Nikoletopoulou V, Markaki M, Palikaras K, Tavernarakis N (2013) Crosstalk between apoptosis, necrosis and autophagy. Biochim Biophys Acta 1833:3448–3459

  56. 56.

    Brune B (2003) Nitric oxide: NO apoptosis or turning it ON? Cell Death Differ 10:864–869

  57. 57.

    Chung HT, Pae HO, Choi BM, Billiar TR, Kim YM (2001) Nitric oxide as a bioregulator of apoptosis. Biochem Biophys Res Commun 282:1075–1079

  58. 58.

    Boyd CS, Cadenas E (2002) Nitric oxide and cell signaling pathways in mitochondrial-dependent apoptosis. Biol Chem 383:411–423

  59. 59.

    Guerrero AD, Schmitz I, Chen M, Wang J (2012) Promotion of caspase activation by caspase-9-mediated feedback amplification of mitochondrial damage. J Clin Cell Immunol 3:1000126

  60. 60.

    Adrain C, Creagh EM, Martin SJ (2001) Apoptosis-associated release of Smac/DIABLO from mitochondria requires active caspases and is blocked by Bcl-2. EMBO J 20:6627–6636

  61. 61.

    Du C, Fang M, Li Y, Li L, Wang X (2000) Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 102:33–42

  62. 62.

    Locksley RM, Killeen N, Lenardo MJ (2001) The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104:487–501

  63. 63.

    Wajant H (2002) The Fas signaling pathway: more than a paradigm. Science 296:1635–1636

  64. 64.

    Strasser A, Jost PJ, Nagata S (2009) The many roles of FAS receptor signaling in the immune system. Immunity 30:180–192

  65. 65.

    Kischkel FC, Hellbardt S, Behrmann I et al (1995) Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor. EMBO J 14:5579–5588

  66. 66.

    Hsu H, Xiong J, Goeddel DV (1995) The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation. Cell 81:495–504

  67. 67.

    Galluzzi L, Brenner C, Morselli E, Touat Z, Kroemer G (2008) Viral control of mitochondrial apoptosis. PLoS Pathog 4:e1000018

  68. 68.

    Zhirnov OP, Klenk HD (2007) Control of apoptosis in influenza virus-infected cells by up-regulation of Akt and p53 signaling. Apoptosis 12:1419–1432

  69. 69.

    Shinada K, Tsukiyama T, Sho T, Okumura F, Asaka M, Hatakeyama S (2011) RNF43 interacts with NEDL1 and regulates p53-mediated transcription. Biochem Biophys Res Commun 404:143–147

  70. 70.

    Nailwal H, Sharma S, Mayank AK, Lal SK (2015) The nucleoprotein of influenza A virus induces p53 signaling and apoptosis via attenuation of host ubiquitin ligase RNF43. Cell Death Dis 6:e1768

  71. 71.

    Mayank AK, Sharma S, Nailwal H, Lal SK (2015) Nucleoprotein of influenza A virus negatively impacts antiapoptotic protein API5 to enhance E2F1-dependent apoptosis and virus replication. Cell Death Dis 6:e2018

  72. 72.

    Tewari M, Yu M, Ross B, Dean C, Giordano A, Rubin R (1997) AAC-11, a novel cDNA that inhibits apoptosis after growth factor withdrawal. Cancer Res 57:4063–4069

  73. 73.

    Jones SE, Jomary C (2002) Clusterin. Int J Biochem Cell Biol 34:427–431

  74. 74.

    Gross A, Jockel J, Wei MC, Korsmeyer SJ (1998) Enforced dimerization of BAX results in its translocation, mitochondrial dysfunction and apoptosis. EMBO J 17:3878–3885

  75. 75.

    Nechushtan A, Smith CL, Hsu YT, Youle RJ (1999) Conformation of the Bax C-terminus regulates subcellular location and cell death. EMBO J 18:2330–2341

  76. 76.

    Jackson D, Killip MJ, Galloway CS, Russell RJ, Randall RE (2010) Loss of function of the influenza A virus NS1 protein promotes apoptosis but this is not due to a failure to activate phosphatidylinositol 3-kinase (PI3 K). Virology 396:94–105

  77. 77.

    Tanaka N, Sato M, Lamphier MS et al (1998) Type I interferons are essential mediators of apoptotic death in virally infected cells. Genes Cells 3:29–37

  78. 78.

    Dianzani F (1975) Viral interference and interferon. Ric Clin Lab 5:196–213

  79. 79.

    Davidson S, Crotta S, McCabe TM, Wack A, Furth AMV (2014) Pathogenic potential of interferon αβ in acute influenza infection. Nat Commun 5:L1315–L1321

  80. 80.

    Davidson S, McCabe TM, Crotta S et al (2016) IFNlambda is a potent anti-influenza therapeutic without the inflammatory side effects of IFNalpha treatment. EMBO Mol Med 8:1099–1112

  81. 81.

    Nacken W, Wixler V, Ehrhardt C, Ludwig S (2017) Influenza A virus NS1 protein-induced JNK activation and apoptosis are not functionally linked. Cell Microbiol 19:e12721

  82. 82.

    Schultz-Cherry S, Dybdahl-Sissoko N, Neumann G, Kawaoka Y, Hinshaw VS (2001) Influenza virus ns1 protein induces apoptosis in cultured cells. J Virol 75:7875–7881

  83. 83.

    Schultz-Cherry S, Hinshaw VS (1996) Influenza virus neuraminidase activates latent transforming growth factor beta. J Virol 70:8624–8629

  84. 84.

    Morris SJ, Price GE, Barnett JM, Hiscox SA, Smith H, Sweet C (1999) Role of neuraminidase in influenza virus-induced apoptosis. J Gen Virol 80(Pt 1):137–146

  85. 85.

    Air GM (2012) Influenza neuraminidase. Influenza Other Respir Viruses 6:245–256

  86. 86.

    Moscona A (2005) Neuraminidase inhibitors for influenza. N Engl J Med 353:1363–1373

  87. 87.

    Chen W, Calvo PA, Malide D et al (2001) A novel influenza A virus mitochondrial protein that induces cell death. Nat Med 7:1306–1312

  88. 88.

    Zamarin D, Garcia-Sastre A, Xiao X, Wang R, Palese P (2005) Influenza virus PB1-F2 protein induces cell death through mitochondrial ANT3 and VDAC1. PLoS Pathog 1:e4

  89. 89.

    Li G, Zhang J, Tong X, Liu W, Ye X (2011) Heat shock protein 70 inhibits the activity of Influenza A virus ribonucleoprotein and blocks the replication of virus in vitro and in vivo. PLoS ONE 6:e16546

  90. 90.

    Halder UC, Bagchi P, Chattopadhyay S, Dutta D, Chawla-Sarkar M (2011) Cell death regulation during influenza A virus infection by matrix (M1) protein: a model of viral control over the cellular survival pathway. Cell Death Dis 2:e197

  91. 91.

    Son K-N, Liang Z, Lipton HL (2015) Double-stranded RNA is detected by immunofluorescence ANALYSIS in RNA and DNA virus infections, including those by negative- stranded RNA viruses. J Virol 89:9383

  92. 92.

    Wang X, Li M, Zheng H et al (2000) Influenza A virus NS1 protein prevents activation of NF-kappaB and induction of alpha/beta interferon. J Virol 74:11566–11573

  93. 93.

    Li W, Moltedo B, Moran TM (2012) Type I interferon induction during influenza virus infection increases susceptibility to secondary Streptococcus pneumoniae infection by negative regulation of gammadelta T cells. J Virol 86:12304–12312

  94. 94.

    Cheng L, Yu H, Li G et al (2017) Type I interferons suppress viral replication but contribute to T cell depletion and dysfunction during chronic HIV-1 infection. JCI Insight 2:e94366

  95. 95.

    Pang IK, Pillai PS, Iwasaki A (2013) Efficient influenza A virus replication in the respiratory tract requires signals from TLR7 and RIG-I. Proc Natl Acad Sci USA 110:13910–13915

  96. 96.

    Barchet W, Krug A, Cella M et al (2005) Dendritic cells respond to influenza virus through TLR7- and PKR-independent pathways. Eur J Immunol 35:236–242

  97. 97.

    Pulendran B, Maddur MS (2015) Innate immune sensing and response to influenza. Curr Top Microbiol Immunol 386:23–71

  98. 98.

    Xagorari A, Chlichlia K (2008) Toll-like receptors and viruses: induction of innate antiviral immune responses. Open Microbiol J 2:49–59

  99. 99.

    Stark GR, Kerr IM, Williams BR, Silverman RH, Schreiber RD (1998) How cells respond to interferons. Annu Rev Biochem 67:227–264

  100. 100.

    Kotredes KP, Gamero AM (2013) Interferons as inducers of apoptosis in malignant cells. J Interferon Cytokine Res 33:162–170

  101. 101.

    Barber GN (2001) Host defense, viruses and apoptosis. Cell Death Differ 8:113–126

  102. 102.

    Talon J, Horvath CM, Polley R et al (2000) Activation of interferon regulatory factor 3 is inhibited by the influenza A virus NS1 protein. J Virol 74:7989–7996

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Correspondence to Lina H. K. Lim.

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Ampomah, P.B., Lim, L.H.K. Influenza A virus-induced apoptosis and virus propagation. Apoptosis 25, 1–11 (2020). https://doi.org/10.1007/s10495-019-01575-3

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Keywords

  • Influenza virus
  • Apoptosis
  • Cell death
  • Virus propagation
  • Interferons