Host immune response to influenza A virus infection

Frontiers in Immunology

Volumn 9, Issue MAR, 2018, Pages

  Chen, Xiaoyong ^a   Liu, Shasha ^b,c   Goraya, Mohsan Ullah ^a   Maarouf, Mohamed ^b,c   Huang, Shile ^d   Chen, Ji Long ^a,b  

^a FUJIAN AGRICULTURE AND FORESTRY UNIVERSITY   (China)

^b INSTITUTE OF MICROBIOLOGY   (China)

^c UNIVERSITY OF CHINESE ACADEMY OF SCIENCES   (China)

^d LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER   (United States)

Author keywords

Adaptive immunity; Immune evasion; Immune response; Influenza A virus; Innate immunity

Indexed keywords

CYTOKINE; HEMAGGLUTININ; IMMUNOGLOBULIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERFERON; INTERFERON REGULATORY FACTOR 3; INTERFERON REGULATORY FACTOR 7; NEUTRALIZING ANTIBODY; TRANSCRIPTION FACTOR; TUMOR NECROSIS FACTOR; VIRUS RECEPTOR;

ADAPTIVE IMMUNITY; CELL MEDIATED CYTOTOXICITY; CELLULAR IMMUNITY; COMPLEMENT ACTIVATION; DENDRITIC CELL; HUMAN; HUMORAL IMMUNITY; IMMUNE RESPONSE; IMMUNOSURVEILLANCE; INFLUENZA A; INFLUENZA A VIRUS; INNATE IMMUNITY; LUNG ALVEOLUS MACROPHAGE; LYMPHOID TISSUE; MEMORY CELL; NONHUMAN; PHAGOCYTE; PLANT IMMUNITY; REVIEW; TRANSCRIPTION INITIATION; VIRUS NEUTRALIZATION;

EID: 85042798206     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2018.00320     Document Type: Review

References (189)

1. Nturibi E, Bhagwat AR, Coburn S, Myerburg MM, Lakdawala SS. Intracellular colocalization of influenza viral RNA and Rab11A is dependent upon microtubule filaments. J Virol (2017) 91(19):e1179-1117. doi:10.1128/jvi.01179-17
2. Cox RJ, Brokstad KA, Ogra P. Influenza virus: immunity and vaccination strategies. Comparison of the immune response to inactivated and live, attenuated influenza vaccines. Scand J Immunol (2004) 59(1):1-15. doi:10.1111/j.0300-9475.2004.01382.x
3. Zhai SL, Zhang H, Chen SN, Zhou X, Lin T, Liu R, et al. Influenza D virus in animal species in Guangdong Province, Southern China. Emerg Infect Dis (2017) 23(8):1392-6. doi:10.3201/eid2308.170059
4. Ghedin E, Sengamalay NA, Shumway M, Zaborsky J, Feldblyum T, Subbu V, et al. Large-scale sequencing of human influenza reveals the dynamic nature of viral genome evolution. Nature (2005) 437(7062):1162-6. doi:10.1038/nature04239
5. Goraya MU, Wang S, Munir M, Chen JL. Induction of innate immunity and its perturbation by influenza viruses. Protein Cell (2015) 6(10):712-21. doi:10.1007/s13238-015-0191-z
6. Vasin AV, Temkina OA, Egorov VV, Klotchenko SA, Plotnikova MA, Kiselev OI. Molecular mechanisms enhancing the proteome of influenza A viruses: an overview of recently discovered proteins. Virus Res (2014) 185(7):53-63. doi:10.1016/j.virusres.2014.03.015
7. Medina RA, García-Sastre A. Influenza A viruses: new research developments. Nat Rev Microbiol (2011) 9(8):590-603. doi:10.1038/nrmicro2613
8. Ma W, Garcíasastre A, Schwemmle M. Expected and unexpected features of the newly discovered bat influenza A-like viruses. PLoS Pathog (2015) 11(6):e1004819. doi:10.1371/journal.ppat.1004819
9. Zeng LY, Yang J, Liu S. Investigational hemagglutinin-targeted influenza virus inhibitors. Expert Opin Investig Drugs (2017) 26(1):63-73. doi:10.1080/13543784.2017.1269170
10. Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA (2003) 289(2):179. doi:10.1001/jama.289.2.179
11. Li J, Yu XF, Pu XY, Xie L, Sun YX, Xiao HX, et al. Environmental connections of novel avian-origin H7N9 influenza virus infection and virus adaptation to the human. Sci China Life Sci (2013) 56(6):485-92. doi:10.1007/s11427-013-4491-3
12. Zhang H, Hale BG, Xu K, Sun B. Viral and host factors required for avian H5N1 influenza A virus replication in mammalian cells. Viruses (2013) 5(6):1431-46. doi:10.3390/v5061431
13. Wang X, Qi S, Ye Z, Ying H, Na S, Du Y, et al. Computational approach for predicting the conserved B-cell epitopes of hemagglutinin H7 subtype influenza virus. Exp Ther Med (2016) 12(4):2439. doi:10.3892/etm.2016.3636
14. Wang S, Li H, Chen Y, Wei H, Gao GF, Liu H, et al. Transport of influenza virus neuraminidase (NA) to host cell surface is regulated by ARHGAP21 and Cdc42 proteins. J Biol Chem (2012) 287(13):9804-16. doi:10.1074/jbc.M111.312959
15. Lin YP, Gregory V, Collins P, Kloess J, Wharton S, Cattle N, et al. Neuraminidase receptor binding variants of human influenza A(H3N2) viruses resulting from substitution of aspartic acid 151 in the catalytic site: a role in virus attachment? J Virol (2010) 84(13):6769. doi:10.1128/JVI.00458-10
16. Zhu X, Mcbride R, Nycholat CM, Yu W, Paulson JC, Wilson IA. Influenza virus neuraminidases with reduced enzymatic activity that avidly bind sialic acid receptors. J Virol (2012) 86(24):13371. doi:10.1128/JVI.01426-12
17. Roy MG, Livraghibutrico A, Fletcher AA, Mcelwee MM, Evans SE, Boerner RM, et al. Muc5b is required for airway defence. Nature (2014) 505(7483):412-6. doi:10.1038/nature12807
18. Ehre C, Worthington EN, Liesman RM, Grubb BR, Barbier D, O'Neal WK, et al. Overexpressing mouse model demonstrates the protective role of Muc5ac in the lungs. Proc Natl Acad Sci U S A (2012) 109(41):16528-33. doi:10.1073/pnas.1206552109
19. Mcauley JL, Corcilius L, Tan HX, Payne RJ, Mcguckin MA, Brown LE. The cell surface mucin MUC1 limits the severity of influenza A virus infection. Mucosal Immunol (2017) 10(6):1581-93. doi:10.1038/mi.2017.16
20. Duez JM, Sixt N, Péchinot A. Influenza virus infection: don't forget the role of the mucociliary system! J Antimicrob Chemother (2009) 63(2):421-2. doi:10.1093/jac/dkn468
21. Cohen M, Zhang XQ, Senaati HP, Chen HW, Varki NM, Schooley RT, et al. Influenza A penetrates host mucus by cleaving sialic acids with neuraminidase. Virol J (2013) 10(1):321. doi:10.1186/1743-422X-10-321
22. Yang J, Liu S, Du L, Jiang S. A new role of neuraminidase (NA) in the influenza virus life cycle: implication for developing NA inhibitors with novel mechanism of action. Rev Med Virol (2016) 26(4):242-50. doi:10.1002/rmv.1879
23. Gulati S, Smith DF, Cummings RD, Couch RB, Griesemer SB, St GK, et al. Human H3N2 influenza viruses isolated from 1968 to 2012 show varying preference for receptor substructures with no apparent consequences for disease or spread. PLoS One (2013) 8(6):e66325. doi:10.1371/journal.pone.0066325
24. Qian W, Wei X, Guo K, Li Y, Lin X, Zou Z, et al. The C-terminal effector domain of non-structural protein 1 of influenza A virus blocks IFN-β production by targeting TNF receptor-associated factor 3. Front Immunol (2017) 8:779. doi:10.3389/fimmu.2017.00779
25. Lam WY, Tang JW, Yeung AC, Chiu LC, Sung JJ, Chan PK. Avian influenza virus A/HK/483/97(H5N1) NS1 protein induces apoptosis in human airway epithelial cells. J Virol (2008) 82(6):2741. doi:10.1128/JVI.01712-07
26. Sugrue RJ, Hay AJ. Structural characteristics of the M2 protein of influenza A viruses: evidence that it forms a tetrameric channel. Virology (1991) 180(2):617. doi:10.1016/0042-6822(91)90075-M
27. Fukuyama S, Kawaoka Y. The pathogenesis of influenza virus infections: the contributions of virus and host factors. Curr Opin Immunol (2011) 23(4):481-6. doi:10.1016/j.coi.2011.07.016
28. Conenello GM, Zamarin D, Perrone LA, Tumpey T, Palese P. A single mutation in the PB1-F2 of H5N1 (HK/97) and 1918 influenza A viruses contributes to increased virulence. PLoS Pathog (2007) 3(10):e141. doi:10.1371/journal.ppat.0030141
29. Wei H, Wang S, Chen Q, Chen Y, Chi X, Zhang L, et al. Suppression of interferon lambda signaling by SOCS-1 results in their excessive production during influenza virus infection. PLoS Pathog (2014) 10(1):e1003845. doi:10.1371/journal.ppat.1003845
30. Van RD, den Bakker MA, Leijten LM, Chutinimitkul S, Munster VJ, de Wit E, et al. Seasonal and pandemic human influenza viruses attach better to human upper respiratory tract epithelium than avian influenza viruses. Am J Pathol (2010) 176(4):1614-8. doi:10.2353/ajpath.2010.090949
31. Shinya K, Ebina M, Yamada S, Ono M, Kasai N, Kawaoka Y. Avian flu: influenza virus receptors in the human airway. Nature (2006) 4(4):321-6. doi:10.1038/440435a
32. Herold S, Becker C, Ridge KM, Budinger GR. Influenza virus-induced lung injury: pathogenesis and implications for treatment. Eur Respir J (2015) 45(5):1463. doi:10.1183/09031936.00186214
33. Hogan BL, Barkauskas CE, Chapman HA, Epstein JA, Jain R, Hsia CC, et al. Repair and regeneration of the respiratory system: complexity, plasticity, and mechanisms of lung stem cell function. Cell Stem Cell (2014) 15(2):123. doi:10.1016/j.stem.2014.07.012
34. Nicholls JM, Chan MCW, Chan WY, Wong HK, Cheung CY, Kwong DLW, et al. Tropism of avian influenza A (H5N1) in the upper and lower respiratory tract. Nat Med (2007) 13(2):147-9. doi:10.1038/nm1529
35. Van RD, Munster VJ, De WE, Rimmelzwaan GF, Fouchier RA, Osterhaus AD, et al. H5N1 virus attachment to lower respiratory tract. Science (2006) 312(5772):399. doi:10.1126/science.1125548
36. Van RD, Munster VJ, De WE, Rimmelzwaan GF, Fouchier RA, Osterhaus AD, et al. Human and avian influenza viruses target different cells in the lower respiratory tract of humans and other mammals. Am J Pathol (2007) 171(4):1215-23. doi:10.2353/ajpath.2007.070248
37. Olofsson S, Kumlin U, Dimock K, Arnberg N. Avian influenza and sialic acid receptors: more than meets the eye? Lancet Infect Dis (2005) 5(3):184-8. doi:10.1016/S1473-3099(05)70026-8
38. Zeng H, Pappas C, Belser JA, Houser KV, Zhong W, Wadford DA, et al. Human pulmonary microvascular endothelial cells support productive replication of highly pathogenic avian influenza viruses: possible involvement in the pathogenesis of human H5N1 virus infection. J Virol (2012) 86(2):667-78. doi:10.1128/JVI.06348-11
39. Kuiken T, Riteau B, Fouchier RA, Rimmelzwaan GF. Pathogenesis of influenza virus infections: the good, the bad and the ugly. Curr Opin Virol (2012) 2(3):276-86. doi:10.1016/j.coviro.2012.02.013
40. Xu R, Mcbride R, Paulson JC, Basler CF, Wilson IA. Structure, receptor binding, and antigenicity of influenza virus hemagglutinins from the 1957 H2N2 pandemic. J Virol (2010) 84(4):1715. doi:10.1128/JVI.02162-09
41. Gao Y, Zhang Y, Shinya K, Deng G, Jiang Y, Li Z, et al. Identification of amino acids in HA and PB2 critical for the transmission of H5N1 avian influenza viruses in a mammalian host. PLoS Pathog (2009) 5(12):e1000709. doi:10.1371/journal.ppat.1000709
42. Xiong X, Martin SR, Haire LF, Wharton SA, Daniels RS, Bennett MS, et al. Receptor binding by an H7N9 influenza virus from humans. Nature (2013) 499(7459):496. doi:10.1038/nature12372
43. Byrdleotis L, Cummings RD, Steinhauer DA. The interplay between the host receptor and influenza virus hemagglutinin and neuraminidase. Int J Mol Sci (2017) 18(7):1541. doi:10.3390/ijms18071541
44. de Graaf M, Fouchier RA. Role of receptor binding specificity in influenza A virus transmission and pathogenesis. EMBO J (2014) 33(8):823-41. doi:10.1002/embj.201387442
45. Chen J, Lee KH, Steinhauer DA, Stevens DJ, Skehel JJ, Wiley DC. Structure of the hemagglutinin precursor cleavage site, a determinant of influenza pathogenicity and the origin of the labile conformation. Cell (1998) 95(3):409. doi:10.1016/S0092-8674(00)81771-7
46. Upham JP, Pickett D, Irimura T, Anders EM, Reading PC. Macrophage receptors for influenza A virus: role of the macrophage galactose-type lectin and mannose receptor in viral entry. J Virol (2010) 84(8):3730-7. doi:10.1128/JVI.02148-09
47. Fontana J, Cardone G, Heymann JB, Winkler DC, Steven AC. Structural changes in influenza virus at low pH characterized by cryo-electron tomography. J Virol (2012) 86(6):2919-29. doi:10.1128/JVI.06698-11
48. Lamb RA, Krug RM. Orthomyxoviridae: the viruses and their replication. In: Knipe DM, Howley PM, Fields BN, editors. Fields Virology. Philadelphia: Lippincott-Raven Press (1996)
49. Flint SJ. Principles of Virology: Molecular Biology, Pathogenesis, and Control. Washington DC: ASM Press (2000). p. 942-3
50. Sun X, Whittaker GR. Entry of influenza virus. Adv Exp Med Biol (2013) 790:72. doi:10.1007/978-1-4614-7651-1_4
51. Cao X. Self-regulation and cross-regulation of pattern-recognition receptor signalling in health and disease. Nat Rev Immunol (2016) 16(1):35. doi:10.1038/nri.2015.8
52. Ouyang J, Zhu X, Chen Y, Wei H, Chen Q, Chi X, et al. NRAV, a long noncoding RNA, modulates antiviral responses through suppression of interferon-stimulated gene transcription. Cell Host Microbe (2014) 16(5):616-26. doi:10.1016/j.chom.2014.10.001
53. Rehwinkel J, Tan CP, Goubau D, Schulz O, Pichlmair A, Bier K, et al. RIG-I detects viral genomic RNA during negative-strand RNA virus infection. Cell (2010) 140(3):397-408. doi:10.1016/j.cell.2010.01.020
54. Baum A, Sachidanandam R, Garcíasastre A. Preference of RIG-I for short viral RNA molecules in infected cells revealed by next-generation sequencing. Proc Natl Acad Sci U S A (2010) 107(37):16303. doi:10.1073/pnas.1005077107
55. Pichlmair A, Schulz O, Tan CP, Näslund TI, Liljeström P, Weber F, et al. RIG-I-mediated antiviral responses to single-stranded RNA bearing 5'-phosphates. Science (2006) 314(5801):997-1001. doi:10.1126/science.1132998
56. Munir M. TRIM proteins: another class of viral victims. Sci Signal (2010) 3(118):jc2. doi:10.1126/scisignal.3118jc2
57. Yoneyama M, Onomoto K, Jogi M, Akaboshi T, Fujita T. Viral RNA detection by RIG-I-like receptors. Curr Opin Immunol (2015) 32:48. doi:10.1016/j.coi.2014.12.012
58. Hiscott J, Lin R, Nakhaei P, Paz S. MasterCARD: a priceless link to innate immunity. Trends Mol Med (2006) 12(2):53-6. doi:10.1016/j.molmed.2005.12.003
59. Takeshita F, Tanaka T, Matsuda T, Tozuka M, Kobiyama K, Saha S, et al. Toll-like receptor adaptor molecules enhance DNA-raised adaptive immune responses against influenza and tumors through activation of innate immunity. J Virol (2006) 80(13):6218. doi:10.1128/JVI.00121-06
60. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on toll-like receptors. Nat Immunol (2010) 11(5):373. doi:10.1038/ni.1863
61. Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell (2010) 140(6):805. doi:10.1016/j.cell.2010.01.022
62. Kumar H, Kawai T, Akira S. Pathogen recognition by the innate immune system. Int Rev Immunol (2011) 30(1):16-34. doi:10.3109/08830185.2010.529976
63. Goubau D, Schlee M, Deddouche S, Pruijssers AJ, Zillinger T, Goldeck M, et al. Antiviral immunity via RIG-I-mediated recognition of RNA bearing 5'-diphosphates. Nature (2014) 514(7522):372-5. doi:10.1038/nature13590
64. Schulz O, Diebold SS, Chen M, Näslund TI, Nolte MA, Alexopoulou L, et al. Toll-like receptor 3 promotes cross-priming to virus-infected cells. Nature (2005) 433(7028):887. doi:10.1038/nature03326
65. Lund JM, Alexopoulou L, Sato A, Karow M, Adams NC, Gale NW, et al. Recognition of single-stranded RNA viruses by toll-like receptor 7. Proc Natl Acad Sci U S A (2004) 101(15):5598-603. doi:10.1073/pnas.0400937101
66. Le Goffic R, Pothlichet J, Vitour D, Fujita T, Meurs E, Chignard M, et al. Cutting edge: influenza A virus activates TLR3-dependent inflammatory and RIG-I-dependent antiviral responses in human lung epithelial cells. J Immunol (2007) 178(6):3368-72. doi:10.4049/jimmunol.178.6.3368
67. Ablasser A, Poeck H, Anz D, Berger M, Schlee M, Kim S, et al. Selection of molecular structure and delivery of RNA oligonucleotides to activate TLR7 versus TLR8 and to induce high amounts of IL-12p70 in primary human monocytes. J Immunol (2009) 182(11):6824. doi:10.4049/jimmunol.0803001
68. Philpott DJ, Sorbara MT, Robertson SJ, Croitoru K, Girardin SE. NOD proteins: regulators of inflammation in health and disease. Nat Rev Immunol (2014) 14(1):9. doi:10.1038/nri3565
69. Guarda G, Zenger M, Yazdi AS, Schroder K, Ferrero I, Menu P, et al. Differential expression of NLRP3 among hematopoietic cells. J Immunol (2011) 186(4):2529-34. doi:10.4049/jimmunol.1002720
70. Pothlichet J, Meunier I, Davis BK, Ting JP, Skamene E, Messling VV, et al. Type I IFN triggers RIG-I/TLR3/NLRP3-dependent inflammasome activation in influenza A virus infected cells. PLoS Pathog (2013) 9(4):e1003256. doi:10.1371/journal.ppat.1003256
71. Martinon F, Mayor A, Tschopp J. The inflammasomes: guardians of the body. Annu Rev Immunol (2009) 27(27):229. doi:10.1146/annurev.immunol.021908.132715
72. Ichinohe T, Pang IK, Iwasaki A. Influenza virus activates inflammasomes via its intracellular M2 ion channel. Nat Immunol (2010) 11(5):404-10. doi:10.1038/ni.1861
73. Mcauley JL, Tate MD, Mackenziekludas CJ, Pinar A, Zeng W, Stutz A, et al. Activation of the NLRP3 inflammasome by IAV virulence protein PB1-F2 contributes to severe pathophysiology and disease. PLoS Pathog (2013) 9(5):e1003392. doi:10.1371/journal.ppat.1003392
74. Shan NC, Xiao WZ, Li L, Bai YR, Bei H, Wen SH, et al. Evolution of IFN-γ in tetrapod vertebrates and its functional characterization in green anole lizard (Anolis carolinensis). Dev Comp Immunol (2016) 61:208. doi:10.1016/j.dci.2016.04.004
75. Wang J, Oberley-Deegan R, Wang S, Nikrad M, Funk C, Hartshorn K, et al. Differentiated human alveolar type II cells secrete antiviral IL-29 (IFN-lambda 1) in response to influenza A infection. J Immunol (2009) 182(3):1296-304. doi:10.4049/jimmunol.182.3.1296
76. Schneider WM, Chevillotte MD, Rice CM. Interferon-stimulated genes: a complex web of host defenses. Annu Rev Immunol (2014) 32(1):513. doi:10.1146/annurev-immunol-032713-120231
77. Mordstein M, Kochs G, Dumoutier L, Renauld JC, Paludan SR, Klucher K, et al. Interferon-γ contributes to innate immunity of mice against influenza A virus but not against hepatotropic viruses. PLoS Pathog (2008) 43(3):e1000151. doi:10.1371/journal.ppat.1000151
78. Crotta S, Davidson S, Mahlakoiv T, Desmet CJ, Buckwalter MR, Albert ML, et al. Type I and type III interferons drive redundant amplification loops to induce a transcriptional signature in influenza-infected airway epithelia. PLoS Pathog (2013) 9(11):e1003773. doi:10.1371/journal.ppat.1003773
79. Davidson S, Mccabe TM, Crotta S, Gad HH, Hessel EM, Beinke S, et al. IFNγ is a potent anti-influenza therapeutic without the inflammatory side effects of IFNa treatment. EMBO Mol Med (2016) 8(9):1099-112. doi:10.15252/emmm.201606413
80. Kim S, Kim MJ, Kim CH, Kang JW, Shin HK, Kim DY, et al. The superiority of IFN-lambda as a therapeutic candidate to control acute influenza viral lung infection. Am J Respir Cell Mol Biol (2016) 56(2):202-12. doi:10.1165/rcmb.2016-0174OC
81. Fernández M, Quiroga JA, Martin J, Herrero M, Pardo M, Horisberger MA, et al. In vivo and in vitro induction of MxA protein in peripheral blood mononuclear cells from patients chronically infected with hepatitis C virus. J Infect Dis (1999) 180(2):262. doi:10.1086/314859
82. Staeheli P, Haller O, Boll W, Lindenmann J, Weissmann C. Mx protein: constitutive expression in 3T3 cells transformed with cloned Mx cDNA confers selective resistance to influenza virus. Cell (1986) 44(1):147. doi:10.1016/0092-8674(86)90493-9
83. Xiao H, Killip MJ, Staeheli P, Randall RE, Jackson D. The human interferon-induced MxA protein inhibits early stages of influenza A virus infection by retaining the incoming viral genome in the cytoplasm. J Virol (2013) 87(23):13053. doi:10.1128/JVI.02220-13
84. Pavlovic J, Haller O, Staeheli P. Human and mouse Mx proteins inhibit different steps of the influenza virus multiplication cycle. J Virol (1992) 66(4):2564
85. Mänz B, Dornfeld D, Götz V, Zell R, Zimmermann P, Haller O, et al. Pandemic influenza A viruses escape from restriction by human MxA through adaptive mutations in the nucleoprotein. PLoS Pathog (2013) 9(3):e1003279. doi:10.1371/journal.ppat.1003279
86. Zimmermann P, Mänz B, Haller O, Schwemmle M, Kochs G. The viral nucleoprotein determines Mx sensitivity of influenza A viruses. J Virol (2011) 85(16):8133-40. doi:10.1128/JVI.00712-11
87. Iwasaki A, Pillai PS. Innate immunity to influenza virus infection. Nat Rev Immunol (2014) 14(5):315-28. doi:10.1038/nri3665
88. Evans SS, Lee DB, Han T, Tomasi TB, Evans RL. Monoclonal antibody to the interferon-inducible protein Leu-13 triggers aggregation and inhibits proliferation of leukemic B cells. Blood (1990) 76(12):2583-93
89. Kelly JM, Gilbert CS, Stark GR, Kerr IM. Differential regulation of interferon-induced mRNAs and c-myc mRNA by alpha-and gamma-interferons. Eur J Biochem (1985) 153(2):367-71. doi:10.1111/j.1432-1033.1985.tb09312.x
90. Brass AL, Huang IC, Benita Y, John SP, Krishnan MN, Feeley EM, et al. The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. Cell (2009) 139(7):1243-54. doi:10.1016/j.cell.2009.12.017
91. Liu SY, Aliyari R, Chikere K, Li G, Marsden MD, Smith JK, et al. Interferon-inducible cholesterol-25-hydroxylase broadly inhibits viral entry by production of 25-hydroxycholesterol. Immunity (2013) 38(1):92-105. doi:10.1016/j.immuni.2012.11.005
92. Blanc M, Hsieh WY, Robertson KA, Kropp KA, Forster T, Shui G, et al. The transcription factor STAT-1 couples macrophage synthesis of 25-hydroxycholesterol to the interferon antiviral response. Immunity (2013) 38(1):106-18. doi:10.1016/j.immuni.2012.11.004
93. Gold ES, Diercks AH, Podolsky I, Podyminogin RL, Askovich PS, Treuting PM, et al. 25-Hydroxycholesterol acts as an amplifier of inflammatory signaling. Proc Natl Acad Sci U S A (2014) 111(29):10666-71. doi:10.1073/pnas.1404271111
94. Gack MU, Shin YC, Joo CH, Urano T, Liang C, Sun L, et al. TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature (2007) 446(7138):916-20. doi:10.1038/nature05732
95. Di Pietro A, Kajaste-Rudnitski A, Oteiza A, Nicora L, Towers GJ, Mechti N, et al. TRIM22 inhibits influenza A virus infection by targeting the viral nucleoprotein for degradation. J Virol (2013) 87(8):4523-33. doi:10.1128/JVI.02548-12
96. Fu B, Wang L, Ding H, Schwamborn JC, Li S, Dorf ME. TRIM32 senses and restricts influenza A virus by ubiquitination of PB1 polymerase. PLoS Pathog (2015) 11(6):e1004960. doi:10.1371/journal.ppat.1004960
97. Tang Q, Wang X, Gao G. The short form of the zinc finger antiviral protein inhibits influenza A virus protein expression and is antagonized by the virus-encoded NS1. J Virol (2017) 91(2):e1909-16. doi:10.1128/jvi.01909-16
98. Liu C-H, Zhou L, Chen G, Krug RM. Battle between influenza A virus and a newly identified antiviral activity of the PARP-containing ZAPL protein. Proc Natl Acad Sci U S A (2015) 112(45):14048-53. doi:10.1073/pnas.1509745112
99. Silverman RH. Viral encounters with 2', 5'-oligoadenylate synthetase and RNase L during the interferon antiviral response. J Virol (2007) 81(23):12720-9. doi:10.1128/jvi.01471-07
100. Ank N, West H, Bartholdy C, Eriksson K, Thomsen AR, Paludan SR. Lambda interferon (IFN-lambda), a type III IFN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo. J Virol (2006) 80(9):4501-9. doi:10.1128/JVI.80.9.4501-4509.2006
101. Dauber B, Martínez-Sobrido L, Schneider J, Hai R, Waibler Z, Kalinke U, et al. Influenza B virus ribonucleoprotein is a potent activator of the antiviral kinase PKR. PLoS Pathog (2009) 5(6):e1000473. doi:10.1371/journal.ppat.1000473
102. Yuan W, Krug RM. Influenza B virus NS1 protein inhibits conjugation of the interferon (IFN)-induced ubiquitin-like ISG15 protein. EMBO J (2001) 20(3):362-71. doi:10.1093/emboj/20.3.362
103. Hu S, Yin L, Mei S, Li J, Xu F, Sun H, et al. BST-2 restricts IAV release and is countered by the viral M2 protein. Biochem J (2017) 474(5):715-30. doi:10.1042/bcj20160861
104. Gnirß K, Zmora P, Blazejewska P, Winkler M, Lins A, Nehlmeier I, et al. Tetherin sensitivity of influenza A viruses is strain specific: role of hemagglutinin and neuraminidase. J Virol (2015) 89(18):9178-88. doi:10.1128/jvi.00615-15
105. Wang X, Hinson ER, Cresswell P. The interferon-inducible protein viperin inhibits influenza virus release by perturbing lipid rafts. Cell Host Microbe (2007) 2(2):96. doi:10.1016/j.chom.2007.06.009
106. Neil SJ, Zang T, Bieniasz PD. Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature (2008) 451(7177):425. doi:10.1038/nature06553
107. Evans DT, Serra-Moreno R, Singh RK, Guatelli JC. BST-2/tetherin: a new component of the innate immune response to enveloped viruses. Trends Microbiol (2010) 18(9):388-96. doi:10.1016/j.tim.2010.06.010
108. Mangeat B, Cavagliotti L, Lehmann M, Gers-Huber G, Kaur I, Thomas Y, et al. Influenza virus partially counteracts restriction imposed by tetherin/BST-2. J Biol Chem (2012) 287(26):22015-29. doi:10.1074/jbc.M111.319996
109. Tumpey TM, Garcia-Sastre A, Taubenberger JK, Palese P, Swayne DE, Pantin-Jackwood MJ, et al. Pathogenicity of influenza viruses with genes from the 1918 pandemic virus: functional roles of alveolar macrophages and neutrophils in limiting virus replication and mortality in mice. J Virol (2005) 79(23):14933-44. doi:10.1128/jvi.79.23.14933-14944.2005
110. Herold S, Von WW, Steinmueller M, Pleschka S, Kuziel WA, Mack M, et al. Alveolar epithelial cells direct monocyte transepithelial migration upon influenza virus infection: impact of chemokines and adhesion molecules. J Immunol (2006) 177(3):1817. doi:10.4049/jimmunol.177.3.1817
111. Mendelson M, Tekoah Y, Zilka A, Gershoni-Yahalom O, Gazit R, Achdout H, et al. NKp46 O-glycan sequences that are involved in the interaction with hemagglutinin type 1 of influenza virus. J Virol (2010) 84(8):3789. doi:10.1128/JVI.01815-09
112. Guo H, Kumar P, Malarkannan S. Evasion of natural killer cells by influenza virus. J Leukoc Biol (2011) 89(2):189-94. doi:10.1189/jlb.0610319
113. van Helden MJ, de Graaf N, Boog CJ, Topham DJ, Zaiss DM, Sijts AJ. The bone marrow functions as the central site of proliferation for long-lived NK cells. J Immunol (2012) 189(5):2333-7. doi:10.4049/jimmunol.1200008
114. Holt PG, Strickland DH, Wikström ME, Jahnsen FL. Regulation of immunological homeostasis in the respiratory tract. Nat Rev Immunol (2008) 8(2):142-52. doi:10.1038/nri2236
115. Bahadoran A, Lee SH, Wang SM, Manikam R, Rajarajeswaran J, Raju CS, et al. Immune responses to influenza virus and its correlation to age and inherited factors. Front Microbiol (2016) 7:1841. doi:10.3389/fmicb.2016.01841
116. Heer AK, Harris NL, Kopf M, Marsland BJ. CD4+ and CD8+ T cells exhibit differential requirements for CCR7-mediated antigen transport during influenza infection. J Immunol (2008) 181(10):6984-94. doi:10.4049/jimmunol.181.10.6984
117. GeurtsvanKessel CH, Willart MA, van Rijt LS, Muskens F, Kool M, Baas C, et al. Clearance of influenza virus from the lung depends on migratory langerin+CD11b-but not plasmacytoid dendritic cells. J Exp Med (2008) 205(7):1621-34. doi:10.1084/jem.20071365
118. Hintzen G, Ohl L, del Rio ML, Rodriguez-Barbosa JI, Pabst O, Kocks JR, et al. Induction of tolerance to innocuous inhaled antigen relies on a CCR7-dependent dendritic cell-mediated antigen transport to the bronchial lymph node. J Immunol (2006) 177(10):7346-54. doi:10.4049/jimmunol.177.10.7346
119. van de Sandt CE, Kreijtz JH, Rimmelzwaan GF. Evasion of influenza A viruses from innate and adaptive immune responses. Viruses (2012) 4(9):1438-76. doi:10.3390/v4091438
120. GeurtsvanKessel CH, Bergen IM, Muskens F, Boon L, Hoogsteden HC, Osterhaus AD, et al. Both conventional and interferon killer dendritic cells have antigen-presenting capacity during influenza virus infection. PLoS One (2009) 4(9):e7187. doi:10.1371/journal.pone.0007187
121. Kreijtz JH, Fouchier RA, Rimmelzwaan GF. Immune responses to influenza virus infection. Virus Res (2011) 162(1-2):19-30. doi:10.1016/j.virusres.2011.09.022
122. Ho AW, Prabhu N, Betts RJ, Ge MQ, Dai X, Hutchinson PE, et al. Lung CD103+ dendritic cells efficiently transport influenza virus to the lymph node and load viral antigen onto MHC class I for presentation to CD8 T cells. J Immunol (2011) 187(11):6011-21. doi:10.4049/jimmunol.1100987
123. Pipkin ME, Sacks JA, Cruz-Guilloty F, Lichtenheld MG, Bevan MJ, Rao A. Interleukin-2 and inflammation induce distinct transcriptional programs that promote the differentiation of effector cytolytic T cells. Immunity (2010) 32(1):79-90. doi:10.1016/j.immuni.2009.11.012
124. Whitmire JK, Tan JT, Whitton JL. Interferon-gamma acts directly on CD8+ T cells to increase their abundance during virus infection. J Exp Med (2005) 201(7):1053-9. doi:10.1084/jem.20041463
125. Egli A, Santer DM, O'Shea D, Barakat K, Syedbasha M, Vollmer M, et al. IL-28B is a key regulator of B-and T-cell vaccine responses against influenza. PLoS Pathog (2014) 10(12):e1004556. doi:10.1371/journal.ppat.1004556
126. van Domselaar R, Bovenschen N. Cell death-independent functions of granzymes: hit viruses where it hurts. Rev Med Virol (2011) 21(5):301-14. doi:10.1002/rmv.697
127. Andrade F. Non-cytotoxic antiviral activities of granzymes in the context of the immune antiviral state. Immunol Rev (2010) 235(1):128-46. doi:10.1111/j.0105-2896.2010.00909.x
128. Allie SR, Randall TD. Pulmonary immunity to viruses. Clin Sci (2017) 131(14):1737-62. doi:10.1042/cs20160259
129. Rangel-Moreno J, Carragher DM, de la Luz Garcia-Hernandez M, Hwang JY, Kusser K, Hartson L, et al. The development of inducible bronchus-associated lymphoid tissue depends on IL-17. Nat Immunol (2011) 12(7):639-46. doi:10.1038/ni.2053
130. van Gisbergen KP, Klarenbeek PL, Kragten NA, Unger PP, Nieuwenhuis MB, Wensveen FM, et al. The costimulatory molecule CD27 maintains clonally diverse CD8(+) T cell responses of low antigen affinity to protect against viral variants. Immunity (2011) 35(1):97-108. doi:10.1016/j.immuni.2011.04.020
131. Grant EJ, Quinones-Parra SM, Clemens EB, Kedzierska K. Human influenza viruses and CD8(+) T cell responses. Curr Opin Virol (2016) 16:132-42. doi:10.1016/j.coviro.2016.01.016
132. Valkenburg SA, Venturi V, Dang T, Bird NL, Doherty PC, Turner SJ, et al. Correction: early priming minimizes the age-related immune compromise of CD8+ T cell diversity and function. PLOS Pathog (2012) 8(2):e1002544. doi:10.1371/journal.ppat.1002544
133. Puleston DJ, Zhang H, Powell TJ, Lipina E, Sims S, Panse I, et al. Autophagy is a critical regulator of memory CD8+ T cell formation. Elife (2014) 3(3):e03706. doi:10.7554/eLife.03706
134. Pizzolla A, Tho N, Smith JM, Brooks AG, Kedzieska K, Heath WR, et al. Resident memory CD8(+) T cells in the upper respiratory tract prevent pulmonary influenza virus infection. Sci Immunol (2017) 2(12):eaam6970. doi:10.1126/sciimmunol.aam6970
135. Van BN, Harty JT. Influenza induced lung Trm: not all memories last forever. Immunol Cell Biol (2017) 95(8):651-5. doi:10.1038/icb.2017.32
136. Dunbar P, Wein AN, McMaster SR, Hayward SL, Kohlmeier JE. Tissue-resident monocytes promote the establishment of lung-resident CD8 T cell memory following influenza infection. J Immunol (2016) 196(1 Suppl):68.7
137. Brown DM, Lee S, Garciahernandez ML, Swain SL. Multifunctional CD4 cells expressing gamma interferon and perforin mediate protection against lethal influenza virus infection. J Virol (2012) 86(12):6792-803. doi:10.1128/JVI.07172-11
138. McKinstry KK, Strutt TM, Kuang Y, Brown DM, Sell S, Dutton RW, et al. Memory CD4+ T cells protect against influenza through multiple synergizing mechanisms. J Clin Invest (2012) 122(8):2847-56. doi:10.1172/jci63689
139. Swain SL, McKinstry KK, Strutt TM. Expanding roles for CD4+ T cells in immunity to viruses. Nat Rev Immunol (2012) 12(2):136-48. doi:10.1038/nri3152
140. Yao Q, Fischer KP, Li L, Agrawal B, Berhane Y, Tyrrell DL, et al. Immunogenicity and protective efficacy of a DNA vaccine encoding a chimeric protein of avian influenza hemagglutinin subtype H5 fused to CD154 (CD40L) in Pekin ducks. Vaccine (2010) 28(51):8147-56. doi:10.1016/j.vaccine.2010.09.081
141. Ingulli E, Mondino A, Khoruts A, Jenkins MK. In vivo detection of dendritic cell antigen presentation to CD4(+) T cells. J Exp Med (1997) 185(12):2133-41. doi:10.1084/jem.185.12.2133
142. Lukens MV, Kruijsen D, Coenjaerts FE, Kimpen JL, van Bleek GM. Respiratory syncytial virus-induced activation and migration of respiratory dendritic cells and subsequent antigen presentation in the lung-draining lymph node. J Virol (2009) 83(14):7235-43. doi:10.1128/jvi.00452-09
143. Magram J, Connaughton SE, Warrier RR, Carvajal DM, Wu CY, Ferrante J, et al. IL-12-deficient mice are defective in IFN gamma production and type 1 cytokine responses. Immunity (1996) 4(5):471-81. doi:10.1016/S1074-7613(00)80413-6
144. Pape KA, Khoruts A, Mondino A, Jenkins MK. Inflammatory cytokines enhance the in vivo clonal expansion and differentiation of antigen-activated CD4+ T cells. J Immunol (1997) 159(2):591-8
145. Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell (2000) 100(6):655-69. doi:10.1016/S0092-8674(00)80702-3
146. Liu SY, Sanchez DJ, Aliyari R, Lu S, Cheng G. Systematic identification of type I and type II interferon-induced antiviral factors. Proc Natl Acad Sci U S A (2012) 109(11):4239-44. doi:10.1073/pnas.1114981109
147. Shu U, Kiniwa M, Wu CY, Maliszewski C, Vezzio N, Hakimi J, et al. Activated T cells induce interleukin-12 production by monocytes via CD40-CD40 ligand interaction. Eur J Immunol (1995) 25(4):1125-8. doi:10.1002/eji.1830250442
148. Stuber E, Strober W, Neurath M. Blocking the CD40L-CD40 interaction in vivo specifically prevents the priming of T helper 1 cells through the inhibition of interleukin 12 secretion. J Exp Med (1996) 183(2):693-8. doi:10.1084/jem.183.2.693
149. Zhu J, Yamane H, Paul WE. Differentiation of effector CD4 T cell populations (*). Annu Rev Immunol (2010) 28:445-89. doi:10.1146/annurev-immunol-030409-101212
150. Lamb JR, Eckels DD, Lake P, Johnson AH, Hartzman RJ, Woody JN. Antigen-specific human T lymphocyte clones: induction, antigen specificity, and MHC restriction of influenza virus-immune clones. J Immunol (1982) 128(1):233-8
151. Mukherjee S, Lindell DM, Berlin AA, Morris SB, Shanley TP, Hershenson MB, et al. IL-17-induced pulmonary pathogenesis during respiratory viral infection and exacerbation of allergic disease. Am J Pathol (2011) 179(1):248-58. doi:10.1016/j.ajpath.2011.03.003
152. La Gruta NL, Turner SJ. T cell mediated immunity to influenza: mechanisms of viral control. Trends Immunol (2014) 35(8):396-402. doi:10.1016/j.it.2014.06.004
153. Rangelmoreno J, Carragher DM, Misra RS, Kusser K, Hartson L, Moquin A, et al. B cells promote resistance to heterosubtypic strains of influenza via multiple mechanisms. J Immunol (2008) 180(1):454-63. doi:10.4049/jimmunol.180.1.454
154. Jegaskanda S, Vandenberg K, Laurie KL, Loh L, Kramski M, Winnall WR, et al. Cross-reactive influenza-specific antibody-dependent cellular cytotoxicity in intravenous immunoglobulin as a potential therapeutic against emerging influenza viruses. J Infect Dis (2014) 210(11):1811. doi:10.1093/infdis/jiu334
155. Seibert CW, Rahmat S, Krause JC, Eggink D, Albrecht RA, Goff PH, et al. Recombinant IgA is sufficient to prevent influenza virus transmission in guinea pigs. J Virol (2013) 87(14):7793-804. doi:10.1128/JVI.00979-13
156. Frasca D, Diaz A, Romero M, Blomberg BB. The generation of memory B cells is maintained, but the antibody response is not, in the elderly after repeated influenza immunizations. Vaccine (2016) 34(25):2834-40. doi:10.1016/j.vaccine.2016.04.023
157. Chen M, Hong MJ, Sun H, Wang L, Shi X, Gilbert BE, et al. Essential role for autophagy in the maintenance of immunological memory against influenza infection. Nat Med (2014) 20(5):503. doi:10.1038/nm.3521
158. Mazanec MB, Coudret CL, Fletcher DR. Intracellular neutralization of influenza virus by immunoglobulin A anti-hemagglutinin monoclonal antibodies. J Virol (1995) 69(2):1339-43
159. Murphy BR, Clements ML. The systemic and mucosal immune response of humans to influenza A virus. Curr Top Microbiol Immunol (1989) 146:107-16
160. Zuercher AW, Coffin SE, Thurnheer MC, Fundova P, Cebra JJ. Nasal-associated lymphoid tissue is a mucosal inductive site for virus-specific humoral and cellular immune responses. J Immunol (2002) 168(4):1796-803. doi:10.4049/jimmunol.168.4.1796
161. Fujimura Y, Takeda M, Ikai H, Haruma K, Akisada T, Harada T, et al. The role of M cells of human nasopharyngeal lymphoid tissue in influenza virus sampling. Virchows Arch (2004) 444(1):36-42. doi:10.1007/s00428-003-0898-8
162. Asanuma H, Thompson AH, Iwasaki T, Sato Y, Inaba Y, Aizawa C, et al. Isolation and characterization of mouse nasal-associated lymphoid tissue. J Immunol Methods (1997) 202(2):123-31. doi:10.1016/S0022-1759(96)00243-8
163. Harty JT, Badovinac VP. Shaping and reshaping CD8+ T-cell memory. Nat Rev Immunol (2008) 8(2):107-19. doi:10.1038/nri2251
164. Wu T, Hu Y, Lee YT, Bouchard KR, Benechet A, Khanna K, et al. Lung-resident memory CD8 T cells (TRM) are indispensable for optimal cross-protection against pulmonary virus infection. J Leukoc Biol (2014) 95(2):215-24. doi:10.1189/jlb.0313180
165. Bienenstock J, Clancy R, Perey D. Bronchus-associated lymphoid tissue (BALT): its relation to mucosal immunity. Immunologic and Infectious Reactions in the Lung, (1976) 1:29-58
166. Mikhak Z, Strassner JP, Luster AD. Lung dendritic cells imprint T cell lung homing and promote lung immunity through the chemokine receptor CCR4. J Exp Med (2013) 210(9):1855-69. doi:10.1084/jem.20130091
167. Chiu C, Ellebedy AH, Wrammert J, Ahmed R. B Cell Responses to Influenza Infection and Vaccination. Cham, ZG: Springer International Publishing (2014). 381 p
168. Van RE, Ainai A, Suzuki T, Hasegawa H. Mucosal IgA responses in influenza virus infections; thoughts for vaccine design. Vaccine (2012) 30(40):5893. doi:10.1016/j.vaccine.2012.04.109
169. Asahi Y, Yoshikawa T, Watanabe I, Iwasaki T, Hasegawa H, Sato Y, et al. Protection against influenza virus infection in polymeric Ig receptor knockout mice immunized intranasally with adjuvant-combined vaccines. J Immunol (2002) 168(6):2930. doi:10.4049/jimmunol.168.6.2930
170. Akira A, Shin-Ichi T, Tadaki S, Elly VR, Ryo I, Takato O, et al. Intranasal vaccination with an inactivated whole influenza virus vaccine induces strong antibody responses in serum and nasal mucus of healthy adults. Hum Vaccin Immunother (2013) 9(9):1962-70. doi:10.4161/hv.25458
171. Suzuki T, Kawaguchi A, Ainai A, Tamura S, Ito R, Multihartina P, et al. Relationship of the quaternary structure of human secretory IgA to neutralization of influenza virus. Proc Natl Acad Sci U S A (2015) 112(25):7809. doi:10.1073/pnas.1503885112
172. Xia C, Vijayan M, Pritzl CJ, Fuchs SY, Mcdermott AB, Hahm B. Hemagglutinin of influenza A virus antagonizes type I interferon (IFN) responses by inducing degradation of type I IFN receptor 1. J Virol (2015) 90(5):2403-17. doi:10.1128/JVI.02749-15
173. Peacock T, Reddy K, James J, Adamiak B, Barclay W, Shelton H, et al. Antigenic mapping of an H9N2 avian influenza virus reveals two discrete antigenic sites and a novel mechanism of immune escape. Sci Rep (2016) 6:18745. doi:10.1038/srep18745
174. Hervé PL, Lorin V, Jouvion G, Da CB, Escriou N. Addition of N-glycosylation sites on the globular head of the H5 hemagglutinin induces the escape of highly pathogenic avian influenza A H5N1 viruses from vaccine-induced immunity. Virology (2015) 486(8):134-45. doi:10.1016/j.virol.2015.08.033
175. Baron Y, Seidel E, Tsukerman P, Mandelboim M, Mandelboim O. Influenza virus uses its neuraminidase protein to evade the recognition of two activating NK cell receptors. J Infect Dis (2014) 210(3):410. doi:10.1093/infdis/jiu094
176. Gack MU, Kirchhofer A, Shin YC, Inn KS, Liang C, Cui S, et al. Roles of RIG-I N-terminal tandem CARD and splice variant in TRIM25-mediated antiviral signal transduction. Proc Natl Acad Sci U S A (2008) 105(43):16743. doi:10.1073/pnas.0804947105
177. Gack MU, Albrecht RA, Urano T, Inn KS, Huang I, Carnero E, et al. Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by RIG-I. Cell Host Microbe (2009) 5(5):439-49. doi:10.1016/j.chom.2009.04.006
178. Kedersha NL, Rome LH. Isolation and characterization of a novel ribonucleoprotein particle: large structures contain a single species of small RNA. J Cell Biol (1986) 103(3):699-709. doi:10.1083/jcb.103.3.699
179. Li F, Chen Y, Zhang Z, Ouyang J, Wang Y, Yan R, et al. Robust expression of vault RNAs induced by influenza A virus plays a critical role in suppression of PKR-mediated innate immunity. Nucleic Acids Res (2015) 43(21):10321-37. doi:10.1093/nar/gkv1078
180. Rückle A, Haasbach E, Julkunen I, Planz O, Ehrhardt C, Ludwig S. The NS1 protein of influenza A virus blocks RIG-I-mediated activation of the noncanonical NF-κB pathway and p52/RelB-dependent gene expression in lung epithelial cells. J Virol (2012) 86(18):10211-7. doi:10.1128/JVI.00323-12
181. Gao S, Song L, Li J, Zhang Z, Peng H, Jiang W, et al. Influenza A virus-encoded NS1 virulence factor protein inhibits innate immune response by targeting IKK. Cell Microbiol (2012) 14(12):1849. doi:10.1111/cmi.12005
182. Jia D, Rahbar R, Chan RW, Lee SM, Chan MC, Wang BX, et al. Influenza virus non-structural protein 1 (NS1) disrupts interferon signaling. PLoS One (2010) 5(11):e13927. doi:10.1371/journal.pone.0013927
183. Fernandez-Sesma A, Marukian S, Ebersole BJ, Kaminski D, Park M-S, Yuen T, et al. Influenza virus evades innate and adaptive immunity via the NS1 protein. J Virol (2006) 80(13):6295-304. doi:10.1128/JVI.02381-05
184. Anastasina M, May NL, Bugai A, Yu F, Söderholm S, Gaelings L, et al. Influenza virus NS1 protein binds cellular DNA to block transcription of antiviral genes. Biochim Biophys Acta (2016) 1859(11):1440-8. doi:10.1016/j.bbagrm.2016.09.005
185. Varga ZT, Ramos I, Hai R, Schmolke M, Garcíasastre A, Fernandezsesma A, et al. The influenza virus protein PB1-F2 inhibits the induction of type I interferon at the level of the MAVS adaptor protein. PLoS Pathog (2011) 7(6):e1002067. doi:10.1371/journal.ppat.1002067
186. Iwai A, Shiozaki T, Kawai T, Akira S, Kawaoka Y, Takada A, et al. Influenza A virus polymerase inhibits type I interferon induction by binding to interferon β promoter stimulator 1. J Biol Chem (2010) 285(42):32064-74. doi:10.1074/jbc.M110.112458
187. Grimm D, Staeheli P, Hufbauer M, Koerner I, Martínez-Sobrido L, Solórzano A, et al. Replication fitness determines high virulence of influenza A virus in mice carrying functional Mx1 resistance gene. Proc Natl Acad Sci U S A (2007) 104(16):6806-11. doi:10.1073/pnas.0701849104
188. Münz C. Influenza A virus lures autophagic protein LC3 to budding sites. Cell Host Microbe (2014) 15(2):130-1. doi:10.1016/j.chom.2014.01.014
189. Beale R, Wise H, Stuart A, Ravenhill B, Digard P, Randow FA. LC3-interacting motif in the influenza A virus M2 protein is required to subvert autophagy and maintain virion stability. Cell Host Microbe (2014) 15(2):239-47. doi:10.1016/j.chom.2014.01.006