Interactions between NS1 of Influenza A Viruses and Interferon-α/β: Determinants for Vaccine Development

Journal of Interferon and Cytokine Research

Volumn 37, Issue 8, 2017, Pages 331-341

  Wang, Ben X ^a,b   Fish, Eleanor N ^a,b  

^a UNIVERSITY HEALTH NETWORK   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

Author keywords

host pathogen interactions; IFN ; influenza A virus; interferon stimulated genes; nonstructural protein 1

Indexed keywords

ALPHA INTERFERON; BETA INTERFERON; GENOMIC RNA; INFLUENZA VACCINE; LIVE VACCINE; NONSTRUCTURAL PROTEIN 1; PATTERN RECOGNITION RECEPTOR; TOLL LIKE RECEPTOR 7; TOLL LIKE RECEPTOR 8; VIRULENCE FACTOR; INS1 PROTEIN, INFLUENZA VIRUS; PROTEIN BINDING; VIRAL PROTEIN;

ANTIVIRAL ACTIVITY; CELL ACTIVATION; CELL DIFFERENTIATION; DISEASE SEVERITY; HOST PATHOGEN INTERACTION; HUMAN; IMMUNOCOMPETENT CELL; INFLUENZA A; INFLUENZA A VIRUS; INFLUENZA VACCINATION; INNATE IMMUNITY; INTERFERON PRODUCTION; MACROPHAGE; NEUTROPHIL; NONHUMAN; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION; VIRUS REPLICATION; ANIMAL; IMMUNOLOGY; METABOLISM;

ANIMALS; HUMANS; INFLUENZA VACCINES; INTERFERON-ALPHA; INTERFERON-BETA; PROTEIN BINDING; VIRAL NONSTRUCTURAL PROTEINS; VIRUS REPLICATION;

EID: 85026919396     PISSN: 10799907     EISSN: 15577465     Source Type: Journal    
DOI: 10.1089/jir.2017.0032     Document Type: Review

References (112)

1. Abdoli A, Soleimanjahi H, Tavassoti Kheiri M, Jamali A, Jamaati A. 2013. Determining influenza virus shedding at different time points in madin-darby canine kidney cell line. Cell J 15(2):130-135.
2. Ablasser A, Poeck H, Anz D, Berger M, Schlee M, Kim S, Bourquin C, Goutagny N, Jiang Z, Fitzgerald KA, Rothenfusser S, Endres S, Hartmann G, Hornung V. 2009. 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 182(11):6824-6833.
3. Allen IC, Scull MA, Moore CB, Holl EK, McElvania-TeKippe E, Taxman DJ, Guthrie EH, Pickles RJ, Ting JP. 2009. The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. Immunity 30(4):556-565.
4. Arimori Y, Nakamura R, Yamada H, Shibata K, Maeda N, Kase T, Yoshikai Y. 2013. Type I interferon limits influenza virusinduced acute lung injury by regulation of excessive inflammation in mice. Antiviral Res 99(3):230-237.
5. Ayllon J, Hale BG, Garcia-Sastre A. 2012. Strain-specific contribution of NS1-activated phosphoinositide 3-kinase signaling to influenza A virus replication and virulence. J Virol 86(9):5366-5370.
6. Bean B, Moore BM, Sterner B, Peterson LR, Gerding DN, Balfour HH, Jr. 1982. Survival of influenza viruses on environmental surfaces. J Infect Dis 146(1):47-51.
7. Benitez AA, PanisM, Xue J, Varble A, Shim JV, Frick AL, Lopez CB, Sachs D, tenOever BR. 2015. In vivo RNAi screening identifies MDA5 as a significant contributor to the cellular defense against influenza A virus. Cell Rep 11(11):1714-1726.
8. Bennett AL, Smith DW, Cummins MJ, Jacoby PA, Cummins JM, Beilharz MW. 2013. Low-dose oral interferon alpha as prophylaxis against viral respiratory illness: a double-blind, parallel controlled trial during an influenza pandemic year. Influenza Other Respir Viruses 7(5):854-862.
9. Bergmann M, Garcia-Sastre A, Carnero E, Pehamberger H, Wolff K, Palese P, Muster T. 2000. Influenza virus NS1 protein counteracts PKR-mediated inhibition of replication. J Virol 74(13):6203-6206.
10. Bhardwaj N, Bender A, Gonzalez N, Bui LK, Garrett MC, Steinman RM. 1994. Influenza virus-infected dendritic cells stimulate strong proliferative and cytolytic responses from human CD8+ T cells. J Clin Invest 94(2):797-807.
11. Brass AL, Huang IC, Benita Y, John SP, Krishnan MN, Feeley EM, Ryan BJ, Weyer JL, van der Weyden L, Fikrig E, Adams DJ, Xavier RJ, Farzan M, Elledge SJ. 2009. The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. Cell 139(7):1243-1254.
12. Chakrabarti A, Banerjee S, Franchi L, Loo YM, Gale M, Jr., Nunez G, Silverman RH. 2015. RNase L activates the NLRP3 inflammasome during viral infections. Cell Host Microbe 17(4):466-477.
13. Chebath J, Benech P, Hovanessian A, Galabru J, Revel M. 1987. Four different forms of interferon-induced 2',5'-oligo(A) synthetase identified by immunoblotting in human cells. J Biol Chem 262(8):3852-3857.
14. Cooper DA, Banerjee S, Chakrabarti A, Garcia-Sastre A, Hesselberth JR, Silverman RH, Barton DJ. 2015. RNase L targets distinct sites in influenza A virus RNAs. J Virol 89(5):2764-2776.
15. Darapaneni V, Prabhaker VK, Kukol A. 2009. Large-scale analysis of influenza A virus sequences reveals potential drug target sites of non-structural proteins. J Gen Virol 90(Pt 9): 2124-2133.
16. Das K, Ma LC, Xiao R, Radvansky B, Aramini J, Zhao L, Marklund J, Kuo RL, Twu KY, Arnold E, Krug RM, Montelione GT. 2008. Structural basis for suppression of a host antiviral response by influenza A virus. Proc Natl Acad Sci U S A 105(35):13093-13098.
17. Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S, Garten RJ, Gubareva LV, Xu X, Bridges CB, Uyeki TM. 2009. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 360(25):2605-2615.
18. de Jong MD, Simmons CP, Thanh TT, Hien VM, Smith GJ, Chau TN, Hoang DM, Chau NV, Khanh TH, Dong VC, Qui PT, Cam BV, Ha do Q, Guan Y, Peiris JS, Chinh NT, Hien TT, Farrar J. 2006. Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nat Med 12(10):1203-1207.
19. Desai TM, Marin M, Chin CR, Savidis G, Brass AL, Melikyan GB. 2014. IFITM3 restricts influenza A virus entry by blocking the formation of fusion pores following virusendosome hemifusion. PLoS Pathog 10(4):e1004048.
20. Diebold SS, Kaisho T, Hemmi H, Akira S, Reis e Sousa C. 2004. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 303(5663):1529-1531.
21. Donovan J, Whitney G, Rath S, Korennykh A. 2015. Structural mechanism of sensing long dsRNA via a noncatalytic domain in human oligoadenylate synthetase 3. Proc Natl Acad Sci U S A 112(13):3949-3954.
22. Falcon AM, Fernandez-Sesma A, Nakaya Y, Moran TM, Ortin J, Garcia-Sastre A. 2005. Attenuation and immunogenicity in mice of temperature-sensitive influenza viruses expressing truncated NS1 proteins. J Gen Virol 86(Pt 10):2817-2821.
23. Ferko B, Stasakova J, Romanova J, Kittel C, Sereinig S, Katinger H, Egorov A. 2004. Immunogenicity and protection efficacy of replication-deficient influenza A viruses with altered NS1 genes. J Virol 78(23):13037-13045.
24. Floyd-Smith G, Slattery E, Lengyel P. 1981. Interferon action: RNA cleavage pattern of a (2'-5')oligoadenylate - dependent endonuclease. Science 212(4498):1030-1032.
25. Fouchier RA, Schneeberger PM, Rozendaal FW, Broekman JM, Kemink SA, Munster V, Kuiken T, Rimmelzwaan GF, Schutten M, Van Doornum GJ, Koch G, Bosman A, Koopmans M, Osterhaus AD. 2004. Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome. Proc Natl Acad Sci U S A 101(5):1356-1361.
26. Gack MU, Albrecht RA, Urano T, Inn KS, Huang IC, Carnero E, Farzan M, Inoue S, Jung JU, Garcia-Sastre A. 2009. Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I. Cell Host Microbe 5(5):439-449.
27. Gao L, Yu S, Chen Q, Duan Z, Zhou J, Mao C, Yu D, Zhu W, Nie J, Hou Y. 2010. A randomized controlled trial of lowdose recombinant human interferons alpha-2b nasal spray to prevent acute viral respiratory infections in military recruits. Vaccine 28(28):4445-4451.
28. Garcia-Sastre A, Durbin RK, Zheng H, Palese P, Gertner R, Levy DE, Durbin JE. 1998a. The role of interferon in influenza virus tissue tropism. J Virol 72(11):8550-8558.
29. Garcia-Sastre A, Egorov A, Matassov D, Brandt S, Levy DE, Durbin JE, Palese P, Muster T. 1998b. Influenza A virus lacking the NS1 gene replicates in interferon-deficient systems. Virology 252(2):324-330.
30. Guillot L, Le Goffic R, Bloch S, Escriou N, Akira S, Chignard M, Si-Tahar M. 2005. Involvement of toll-like receptor 3 in the immune response of lung epithelial cells to double-stranded RNA and influenza A virus. J Biol Chem 280(7):5571-5580.
31. Hatada E, Saito S, Fukuda R. 1999. Mutant influenza viruses with a defective NS1 protein cannot block the activation of PKR in infected cells. J Virol 73(3):2425-2433.
32. Haye K, Burmakina S, Moran T, Garcia-Sastre A, Fernandez-Sesma A. 2009. The NS1 protein of a human influenza virus inhibits type I interferon production and the induction of antiviral responses in primary human dendritic and respiratory epithelial cells. J Virol 83(13):6849-6862.
33. Heer AK, Shamshiev A, Donda A, Uematsu S, Akira S, Kopf M, Marsland BJ. 2007. TLR signaling fine-tunes antiinfluenza B cell responses without regulating effector T cell responses. J Immunol 178(4):2182-2191.
34. Hovanessian AG, Svab J, Marie I, Robert N, Chamaret S, Laurent AG. 1988. Characterization of 69-and 100-kDa forms of 2-5A-synthetase from interferon-treated human cells. J Biol Chem 263(10):4945-4949.
35. Hsiang TY, Zhao C, Krug RM. 2009. Interferon-induced ISG15 conjugation inhibits influenza A virus gene expression and replication in human cells. J Virol 83(12):5971-5977.
36. Huang IC, Bailey CC, Weyer JL, Radoshitzky SR, Becker MM, Chiang JJ, Brass AL, Ahmed AA, Chi X, Dong L, Longobardi LE, Boltz D, Kuhn JH, Elledge SJ, Bavari S, Denison MR, Choe H, Farzan M. 2011. Distinct patterns of IFITMmediated restriction of filoviruses, SARS coronavirus, and influenza A virus. PLoS Pathog 7(1):e1001258.
37. Ichinohe T, Pang IK, Iwasaki A. 2010. Influenza virus activates inflammasomes via its intracellular M2 ion channel. Nat Immunol 11(5):404-410.
38. Jewell NA, Vaghefi N, Mertz SE, Akter P, Peebles RS, Jr., Bakaletz LO, Durbin RK, Flano E, Durbin JE. 2007. Differential type I interferon induction by respiratory syncytial virus and influenza a virus in vivo. J Virol 81(18):9790-9800.
39. Jia D, Rahbar R, Chan RW, Lee SM, Chan MC, Wang BX, Baker DP, Sun B, Peiris JS, Nicholls JM, Fish EN. 2010. Influenza virus non-structural protein 1 (NS1) disrupts interferon signaling. PLoS One 5(11):e13927.
40. Jureka AS, Kleinpeter AB, Cornilescu G, Cornilescu CC, Petit CM. 2015. Structural basis for a novel interaction between the NS1 protein derived from the 1918 influenza virus and RIG-I. Structure 23(11):2001-2010.
41. Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K, Uematsu S, Jung A, Kawai T, Ishii KJ, Yamaguchi O, Otsu K, Tsujimura T, Koh CS, Reis e Sousa C, Matsuura Y, Fujita T, Akira S. 2006. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 441(7089):101-105.
42. Klein MB, Lu Y, DelBalso L, Cote S, Boivin G. 2007. Influenzavirus infection is a primary cause of febrile respiratory illness in HIV-infected adults, despite vaccination. Clin Infect Dis 45(2):234-240.
43. Kochs G, Garcia-Sastre A, Martinez-Sobrido L. 2007. Multiple anti-interferon actions of the influenza A virus NS1 protein. J Virol 81(13):7011-7021.
44. Kochs G, Martinez-Sobrido L, Lienenklaus S, Weiss S, Garcia-Sastre A, Staeheli P. 2009. Strong interferon-inducing capacity of a highly virulent variant of influenza A virus strain PR8 with deletions in the NS1 gene. J Gen Virol 90(Pt 12): 2990-2994.
45. Kochs G, Reichelt M, Danino D, Hinshaw JE, Haller O. 2005. Assay and functional analysis of dynamin-like Mx proteins. Methods Enzymol 404:632-643.
46. Koerner I, Kochs G, Kalinke U, Weiss S, Staeheli P. 2007. Protective role of beta interferon in host defense against influenza A virus. J Virol 81(4):2025-2030.
47. Koyama S, Ishii KJ, Kumar H, Tanimoto T, Coban C, Uematsu S, Kawai T, Akira S. 2007. Differential role of TLR-and RLR-signaling in the immune responses to influenza A virus infection and vaccination. J Immunol 179(7):4711-4720.
48. Kugel D, Kochs G, Obojes K, Roth J, Kobinger GP, Kobasa D, Haller O, Staeheli P, von Messling V. 2009. Intranasal administration of alpha interferon reduces seasonal influenza A virus morbidity in ferrets. J Virol 83(8):3843-3851.
49. Le Goffic R, Balloy V, Lagranderie M, Alexopoulou L, Escriou N, Flavell R, Chignard M, Si-Tahar M. 2006. Detrimental contribution of the Toll-like receptor (TLR)3 to influenza A virus-induced acute pneumonia. PLoS Pathog 2(6):e53.
50. Le Goffic R, Pothlichet J, Vitour D, Fujita T, Meurs E, Chignard M, Si-Tahar M. 2007. Cutting Edge: influenza A virus activates TLR3-dependent inflammatory and RIG-Idependent antiviral responses in human lung epithelial cells. J Immunol 178(6):3368-3372.
51. Lenschow DJ, Lai C, Frias-Staheli N, Giannakopoulos NV, Lutz A, Wolff T, Osiak A, Levine B, Schmidt RE, Garcia-Sastre A, Leib DA, Pekosz A, Knobeloch KP, Horak I, Virgin HWt. 2007. IFN-stimulated gene 15 functions as a critical antiviral molecule against influenza, herpes, and Sindbis viruses. Proc Natl Acad Sci U S A 104(4):1371-1376.
52. Li G, Xiang Y, Sabapathy K, Silverman RH. 2004. An apoptotic signaling pathway in the interferon antiviral response mediated by RNase L and c-Jun NH2-terminal kinase. J Biol Chem 279(2):1123-1131.
53. Li S, Min JY, Krug RM, Sen GC. 2006a. Binding of the influenza A virus NS1 protein to PKR mediates the inhibition of its activation by either PACT or double-stranded RNA. Virology 349(1):13-21.
54. Li S, Peters GA, Ding K, Zhang X, Qin J, Sen GC. 2006b. Molecular basis for PKR activation by PACT or dsRNA. Proc Natl Acad Sci U S A 103(26):10005-10010.
55. Liniger M, Summerfield A, Zimmer G, McCullough KC, Ruggli N. 2012. Chicken cells sense influenza A virus infection through MDA5 and CARDIF signaling involving LGP2. J Virol 86(2):705-717.
56. Loeb KR, Haas AL. 1992. The interferon-inducible 15-kDa ubiquitin homolog conjugates to intracellular proteins. J Biol Chem 267(11):7806-7813.
57. Loo YM, Fornek J, Crochet N, Bajwa G, Perwitasari O, Martinez-Sobrido L, Akira S, Gill MA, Garcia-Sastre A, Katze MG, Gale M, Jr. 2008. Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. J Virol 82(1): 335-345.
58. Ludwig S, Wang X, Ehrhardt C, Zheng H, Donelan N, Planz O, Pleschka S, Garcia-Sastre A, Heins G, Wolff T. 2002. The influenza A virus NS1 protein inhibits activation of Jun Nterminal kinase and AP-1 transcription factors. J Virol 76(21): 11166-11171.
59. Lupfer C, Thomas PG, Kanneganti TD. 2014. Nucleotide oligomerization and binding domain 2-dependent dendritic cell activation is necessary for innate immunity and optimal CD8+ T cell responses to influenza A virus infection. J Virol 88(16):8946-8955.
60. Malakhova OA, Yan M, Malakhov MP, Yuan Y, Ritchie KJ, Kim KI, Peterson LF, Shuai K, Zhang DE. 2003. Protein ISGylation modulates the JAK-STAT signaling pathway. Genes Dev 17(4):455-460.
61. Malathi K, Dong B, Gale M, Jr., Silverman RH. 2007. Small self-RNA generated by RNase L amplifies antiviral innate immunity. Nature 448(7155):816-819.
62. Manicassamy B,Manicassamy S, Belicha-Villanueva A, Pisanelli G, Pulendran B, Garcia-Sastre A. 2010. Analysis of in vivo dynamics of influenza virus infection in mice using a GFP reporter virus. Proc Natl Acad Sci U S A 107(25):11531-11536.
63. Melen K, Kinnunen L, Fagerlund R, Ikonen N, Twu KY, Krug RM, Julkunen I. 2007. Nuclear and nucleolar targeting of influenza A virus NS1 protein: striking differences between different virus subtypes. J Virol 81(11):5995-6006.
64. Mibayashi M, Martinez-Sobrido L, Loo YM, Cardenas WB, Gale M, Jr., Garcia-Sastre A. 2007. Inhibition of retinoic acid-inducible gene I-mediated induction of beta interferon by the NS1 protein of influenza A virus. J Virol 81(2):514-524.
65. Min JY, Krug RM. 2006. The primary function of RNA binding by the influenza A virus NS1 protein in infected cells: inhibiting the 2'-5' oligo (A) synthetase/RNase L pathway. Proc Natl Acad Sci U S A 103(18):7100-7105.
66. Min JY, Li S, Sen GC, Krug RM. 2007. A site on the influenza A virus NS1 protein mediates both inhibition of PKR activation and temporal regulation of viral RNA synthesis. Virology 363(1):236-243.
67. Molinari NA, Ortega-Sanchez IR, Messonnier ML, Thompson WW, Wortley PM, Weintraub E, Bridges CB. 2007. The annual impact of seasonal influenza in the US: measuring disease burden and costs. Vaccine 25(27):5086-5096.
68. Mordstein M, Kochs G, Dumoutier L, Renauld JC, Paludan SR, Klucher K, Staeheli P. 2008. Interferon-lambda contributes to innate immunity of mice against influenza A virus but not against hepatotropic viruses. PLoS Pathog 4(9):e1000151.
69. Nigg PE, Pavlovic J. 2015. Oligomerization and GTP-binding Requirements of MxA for viral target recognition and antiviral activity against influenza A virus. J Biol Chem 290(50): 29893-29906.
70. Noti JD, Lindsley WG, Blachere FM, Cao G, Kashon ML, Thewlis RE, McMillen CM, King WP, Szalajda JV, Beezhold DH. 2012. Detection of infectious influenza virus in cough aerosols generated in a simulated patient examination room. Clin Infect Dis 54(11):1569-1577.
71. Onomoto K, Jogi M, Yoo JS, Narita R, Morimoto S, Takemura A, Sambhara S, Kawaguchi A, Osari S, Nagata K, Matsumiya T, Namiki H, Yoneyama M, Fujita T. 2012. Critical role of an antiviral stress granule containing RIG-I and PKR in viral detection and innate immunity. PLoS One 7(8):e43031.
72. Pauli EK, Schmolke M, Wolff T, Viemann D, Roth J, Bode JG, Ludwig S. 2008. Influenza A virus inhibits type I IFN signaling via NF-kappaB-dependent induction of SOCS-3 expression. PLoS Pathog 4(11):e1000196.
73. Peiris JS, Yu WC, Leung CW, Cheung CY, Ng WF, Nicholls JM, Ng TK, Chan KH, Lai ST, Lim WL, Yuen KY, Guan Y. 2004. Re-emergence of fatal human influenza A subtype H5N1 disease. Lancet 363(9409):617-619.
74. Pichlmair A, Schulz O, Tan CP, Naslund TI, Liljestrom P, Weber F, Reis e Sousa C. 2006. RIG-I-mediated antiviral responses to single-stranded RNA bearing 5'-phosphates. Science 314(5801):997-1001.
75. Pirhonen J, Sareneva T, Kurimoto M, Julkunen I, Matikainen S. 1999. Virus infection activates IL-1 beta and IL-18 production in human macrophages by a caspase-1-dependent pathway. J Immunol 162(12):7322-7329.
76. Rajsbaum R, Albrecht RA, Wang MK, Maharaj NP, Versteeg GA, Nistal-Villan E, Garcia-Sastre A, Gack MU. 2012. Species-specific inhibition of RIG-I ubiquitination and IFN induction by the influenza A virus NS1 protein. PLoS Pathog 8(11):e1003059.
77. Ramos I, Carnero E, Bernal-Rubio D, Seibert CW, Westera L, Garcia-Sastre A, Fernandez-Sesma A. 2013. Contribution of double-stranded RNA and CPSF30 binding domains of influenza virus NS1 to the inhibition of type I interferon production and activation of human dendritic cells. J Virol 87(5):2430-2440.
78. Rohani P, Breban R, Stallknecht DE, Drake JM. 2009. Environmental transmission of low pathogenicity avian influenza viruses and its implications for pathogen invasion. Proc Natl Acad Sci U S A 106(25):10365-10369.
79. Ruckle A, Haasbach E, Julkunen I, Planz O, Ehrhardt C, Ludwig S. 2012. The NS1 protein of influenza A virus blocks RIG-I-mediated activation of the noncanonical NF-kappaB pathway and p52/RelB-dependent gene expression in lung epithelial cells. J Virol 86(18):10211-10217.
80. Rusch L, Zhou A, Silverman RH. 2000. Caspase-dependent apoptosis by 2',5'-oligoadenylate activation of RNase L is enhanced by IFN-beta. J Interferon Cytokine Res 20(12): 1091-1100.
81. Rusinova I, Forster S, Yu S, Kannan A, Masse M, Cumming H, Chapman R, Hertzog PJ. 2013. Interferome v2.0: an updated database of annotated interferon-regulated genes. Nucleic Acids Res 41(Database issue):D1040-D1046.
82. Sabbah A, Chang TH, Harnack R, Frohlich V, Tominaga K, Dube PH, Xiang Y, Bose S. 2009. Activation of innate immune antiviral responses by Nod2. Nat Immunol 10(10): 1073-1080.
83. Seo SU, Kwon HJ, Ko HJ, Byun YH, Seong BL, Uematsu S, Akira S, Kweon MN. 2011. Type I interferon signaling regulates Ly6C(hi) monocytes and neutrophils during acute viral pneumonia in mice. PLoS Pathog 7(2):e1001304.
84. Shapiro GI, Gurney T, Jr., Krug RM. 1987. Influenza virus gene expression: control mechanisms at early and late times of infection and nuclear-cytoplasmic transport of virus-specific RNAs. J Virol 61(3):764-773.
85. Shi HX, Yang K, Liu X, Liu XY, Wei B, Shan YF, Zhu LH, Wang C. 2010. Positive regulation of interferon regulatory factor 3 activation by Herc5 via ISG15 modification. Mol Cell Biol 30(10):2424-2436.
86. Shin DL, Hatesuer B, Bergmann S, Nedelko T, Schughart K. 2015. Protection from severe influenza virus infections in mice carrying the Mx1 influenza virus resistance gene strongly depends on genetic background. J Virol 89(19):9998-10009.
87. Shinde V, Bridges CB, Uyeki TM, Shu B, Balish A, Xu X, Lindstrom S, Gubareva LV, Deyde V, Garten RJ, Harris M, Gerber S, Vagasky S, Smith F, Pascoe N, Martin K, Dufficy D, Ritger K, Conover C, Quinlisk P, Klimov A, Bresee JS, Finelli L. 2009. Triple-reassortant swine influenza A (H1) in humans in the United States, 2005-2009. N Engl J Med 360(25):2616-2625.
88. Staeheli P, Grob R, Meier E, Sutcliffe JG, Haller O. 1988. Influenza virus-susceptible mice carry Mx genes with a large deletion or a nonsense mutation. Mol Cell Biol 8(10):4518-4523.
89. Szretter KJ, Gangappa S, Belser JA, Zeng H, Chen H, Matsuoka Y, Sambhara S, Swayne DE, Tumpey TM, Katz JM. 2009. Early control of H5N1 influenza virus replication by the type I interferon response in mice. J Virol 83(11):5825-5834.
90. Talon J, Salvatore M, O'Neill RE, Nakaya Y, Zheng H, Muster T, Garcia-Sastre A, Palese P. 2000. Influenza A and B viruses expressing altered NS1 proteins: a vaccine approach. Proc Natl Acad Sci U S A 97(8):4309-4314.
91. Tate MD, Pickett DL, van Rooijen N, Brooks AG, Reading PC. 2010. Critical role of airway macrophages in modulating disease severity during influenza virus infection of mice. J Virol 84(15):7569-7580.
92. Teijaro JR, Walsh KB, Cahalan S, Fremgen DM, Roberts E, Scott F, Martinborough E, Peach R, Oldstone MB, Rosen H. 2011. Endothelial cells are central orchestrators of cytokine amplification during influenza virus infection. Cell 146(6):980-991.
93. Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, Fukuda K. 2003. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA 289(2):179-186.
94. Tumpey TM, Szretter KJ, Van Hoeven N, Katz JM, Kochs G, Haller O, Garcia-Sastre A, Staeheli P. 2007. The Mx1 gene protects mice against the pandemic 1918 and highly lethal human H5N1 influenza viruses. J Virol 81(19):10818-10821.
95. Twu KY, Noah DL, Rao P, Kuo RL, Krug RM. 2006. The CPSF30 binding site on the NS1A protein of influenza A virus is a potential antiviral target. J Virol 80(8):3957-3965.
96. Uetani K, Hiroi M, Meguro T, Ogawa H, Kamisako T, Ohmori Y, Erzurum SC. 2008. Influenza A virus abrogates IFN-gamma response in respiratory epithelial cells by disruption of the Jak/Stat pathway. Eur J Immunol 38(6):1559-1573.
97. Verhelst J, Parthoens E, Schepens B, Fiers W, Saelens X. 2012. Interferon-inducible protein Mx1 inhibits influenza virus by interfering with functional viral ribonucleoprotein complex assembly. J Virol 86(24):13445-13455.
98. Vilchez RA, McCurry K, Dauber J, Lacono A, Griffith B, Fung J, Kusne S. 2002. Influenza virus infection in adult solid organ transplant recipients. Am J Transplant 2(3):287-291.
99. Wacheck V, Egorov A, Groiss F, Pfeiffer A, Fuereder T, Hoeflmayer D, Kundi M, Popow-Kraupp T, Redlberger-Fritz M, Mueller CA, Cinatl J, Michaelis M, Geiler J, Bergmann M, Romanova J, Roethl E, Morokutti A, Wolschek M, Ferko B, Seipelt J, Dick-Gudenus R, Muster T. 2010. A novel type of influenza vaccine: safety and immunogenicity of replication-deficient influenza virus created by deletion of the interferon antagonist NS1. J Infect Dis 201(3):354-362.
100. Wang J, Nikrad MP, Travanty EA, Zhou B, Phang T, Gao B, Alford T, Ito Y, Nahreini P, Hartshorn K, Wentworth D, Dinarello CA, Mason RJ. 2012. Innate immune response of human alveolar macrophages during influenza A infection. PLoS One 7(3):e29879.
101. Wang JP, Bowen GN, Padden C, Cerny A, Finberg RW, Newburger PE, Kurt-Jones EA. 2008. Toll-like receptormediated activation of neutrophils by influenza A virus. Blood 112(5):2028-2034.
102. Wang X, Hinson ER, Cresswell P. 2007. The interferoninducible protein viperin inhibits influenza virus release by perturbing lipid rafts. Cell Host Microbe 2(2):96-105.
103. Wang X, Li M, Zheng H, Muster T, Palese P, Beg AA, Garcia-Sastre A. 2000. Influenza A virus NS1 protein prevents activation of NF-kappaB and induction of alpha/beta interferon. J Virol 74(24):11566-11573.
104. Wei L, Cui J, Song Y, Zhang S, Han F, Yuan R, Gong L, Jiao P, Liao M. 2014. Duck MDA5 functions in innate immunity against H5N1 highly pathogenic avian influenza virus infections. Vet Res 45:66.
105. WHO. 2016. Influenza (Seasonal) Fact Sheet N211. www.who.int/mediacentre/factsheets/fs211/en (Accessed March 20, 2017).
106. Wreschner DH, James TC, Silverman RH, Kerr IM. 1981. Ribosomal RNA cleavage, nuclease activation and 2-5A(ppp(A2'p)nA) in interferon-treated cells. Nucleic Acids Res 9(7):1571-1581.
107. Yang X, Chang HY, Baltimore D. 1998. Autoproteolytic activation of pro-caspases by oligomerization. Mol Cell 1(2): 319-325.
108. Yoo JK, Baker DP, Fish EN. 2010. Interferon-beta modulates type 1 immunity during influenza virus infection. Antiviral Res 88(1):64-71.
109. Yuan W, Krug RM. 2001. Influenza B virus NS1 protein inhibits conjugation of the interferon (IFN)-induced ubiquitinlike ISG15 protein. EMBO J 20(3):362-371.
110. Yuen KY, Chan PK, Peiris M, Tsang DN, Que TL, Shortridge KF, Cheung PT, To WK, Ho ET, Sung R, Cheng AF. 1998. Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus. Lancet 351(9101):467-471.
111. Zhao C, Hsiang TY, Kuo RL, Krug RM. 2010. ISG15 conjugation system targets the viral NS1 protein in influenza A virusinfected cells. Proc Natl Acad Sci U S A 107(5):2253-2258.
112. Zhou A, Hassel BA, Silverman RH. 1993. Expression cloning of 2-5A-dependent RNAase: a uniquely regulated mediator of interferon action. Cell 72(5):753-765.