簡易檢索 / 詳目顯示

回結果列表
研究生： 戴思平
Tai, Szu-Ping
論文名稱： A 型流感病毒H3N2亞型非結構性蛋白1之基因差異對病毒特性的影響
The effect of NS1 genetic variations on H3N2 influenza A virus properties
指導教授： 王貞仁
Wang, Jen-Reng
學位類別： 碩士
Master
系所名稱： 醫學院 - 醫學檢驗生物技術學系
Department of Medical Laboratory Science and Biotechnology
論文出版年： 2021
畢業學年度： 109
語文別： 英文
論文頁數： 68
中文關鍵詞： 流感病毒 、非結構性蛋白1 、拮抗宿主免疫反應
外文關鍵詞： Influenza virus, NS1, counteract host immune responses
相關次數： 點閱：173  下載：0 
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報
    • 摘要 I Abstract II Acknowledgements IV Table of contents V List of tables VIII List of figures IX List of appendix figures X Abbreviations XI Chapter 1 Introduction 1 1.1 Introduction of influenza viruses 1 1.1.1 Classification and structure of influenza viruses 1 1.1.2 Epidemiology and clinical manifestations of influenza viruses 1 1.1.3 Evolution of influenza A viruses 1 1.2 Influenza virus replication cycle 2 1.2.1 Virus attachment and fusion 2 1.2.2 Virus replication transcription and translation 3 1.2.3 Assembly and budding of virus particles 4 1.2.4 Immunomodulation of virus non-structural protein 4 1.3 Significance of genetic changes in influenza A virus 5 1.3.1 Surface protein gene alteration 5 1.3.2 Internal protein gene evolution 6 1.4 Host innate immune response against influenza virus infection 6 1.5 Characteristics of Influenza non-structural protein 1 (NS1) 7 1.5.1 Sequences, structure and functional domain of NS1 7 1.5.2 Function of NS1 8 1.6 Specific aims 10 Chapter 2 Materials and Methods 12 2.1 Materials 12 2.1.1 Cell line 12 2.1.2 Competent cell 12 2.1.3 Primers 12 2.1.4 Plasmids 13 2.1.5 Enzymes 13 2.1.6 Chemicals and reagents 14 2.1.7 Buffers and solutions 15 2.1.8 Kits 15 2.1.9 Antibodies 16 2.1.10 Instruments 16 2.2 Methods 17 2.2.1 Cell culture 17 2.2.2 NS1 sequencing 17 2.2.3 Phylogenetic analysis 17 2.2.4 Construction of NS1 expression plasmid 18 2.2.5 Generation of reverse genetics viruses 18 2.2.6 IFN-β reporter assay 18 2.2.7 Western blotting 19 2.2.8 Plaque assay 19 2.2.9 Virus growth kinetics 19 2.2.10 Quantitative RT-PCR 20 2.2.11 IFN-sensitivity assay 20 2.2.12 IFN-β ELISA 20 2.2.13 Statistical Analysis 21 Chapter 3 Results 22 3.1 Genetic evolution of H3N2 NS1 gene of NCKUH isolates from 1999 to 2019 22 3.1.1 Collection of NS1 gene sequences of H3N2 viruses 22 3.1.2 Phylogenetic analysis of NS1 gene 22 3.1.3. Analysis of NS1 amino acid substitutions 23 3.2 Determining the effects of genetic variations on NS1 function 23 3.2.1 Analyzing the effect of NS1 substitutions on inhibiting IFN-β promoter activation 23 3.2.2 Generation of reverse genetics viruses 24 3.2.3 Analysis of genetic variations of NS1 on virus’ inhibition of IFN-β promoter activation 24 3.2.4 Analyze the effect of substitutions on NS1 inhibition of IFN-β protein production 26 3.2.5 Analyze the effect of NS1 substitutions on inhibition of IFN-β downstream interferon stimulated genes (ISGs) transcription 26 3.3 To determine whether NS1 genetic variation affects viral properties 27 3.3.1 Analyze the impact of NS1 substitutions on viral growth in A549 cells 27 3.3.2 Analyze the impact of NS1 substitutions on virus sensitivity to IFN 27 3.3.3 Analyze the impact of NS1 substitutions on viral growth in Vero cells 27 Chapter 4 Discussion and Conclusions 29 References 33

    1. Abed Y, Goyette N, Boivin G. 2005. Generation and characterization of recombinant influenza A (H1N1) viruses harboring amantadine resistance mutations. Antimicrobial Agents and Chemotherapy 49:556-9.
    2. Allen JD, Ross TM. 2018. H3N2 influenza viruses in humans: Viral mechanisms, evolution, and evaluation. Human Vaccines & Immunotherapeutics 14:1840-1847.
    3. Aramini JM, Ma LC, Zhou L, Schauder CM, Hamilton K, Amer BR, Mack TR, Lee HW, Ciccosanti CT, Zhao L, Xiao R, Krug RM, Montelione GT. 2011. Dimer interface of the effector domain of non-structural protein 1 from influenza A virus: an interface with multiple functions. Journal of Biological Chemistry 286:26050-60.
    4. 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. Journal of Virology 86:5366-70.
    5. Ayllon J, Russell RJ, Garcia-Sastre A, Hale BG. 2012. Contribution of NS1 effector domain dimerization to influenza A virus replication and virulence. Journal of Virology 86:13095-8.
    6. Ayllon J, Garcia-Sastre A. 2015. The NS1 protein: a multitasking virulence factor. Current Topics in Microbiology and Immunology 386:73-107.
    7. Bouvier NM, Palese P. 2008. The biology of influenza viruses. Vaccine 26 Suppl 4:D49-53.
    8. Burgui I, Aragon T, Ortin J, Nieto A. 2003. PABP1 and eIF4GI associate with influenza virus NS1 protein in viral mRNA translation initiation complexes. Journal of General Virology 84:3263-3274.
    9. Carrillo B, Choi JM, Bornholdt ZA, Sankaran B, Rice AP, Prasad BV. 2014. The influenza A virus protein NS1 displays structural polymorphism. Journal of Virology 88:4113-22.
    10. Chan JF, To KK, Tse H, Jin DY, Yuen KY. 2013. Interspecies transmission and emergence of novel viruses: lessons from bats and birds. Trends in Microbiology 21:544-55.
    11. Chen BJ, Takeda M, Lamb RA. 2005. Influenza virus hemagglutinin (H3 subtype) requires palmitoylation of its cytoplasmic tail for assembly: M1 proteins of two subtypes differ in their ability to support assembly. Journal of Virology 79:13673-84.
    12. Chen G, Liu CH, Zhou L, Krug RM. 2014. Cellular DDX21 RNA helicase inhibits influenza A virus replication but is counteracted by the viral NS1 protein. Cell Host & Microbe 15:484-93.
    13. Chen W, Calvo PA, Malide D, Gibbs J, Schubert U, Bacik I, Basta S, O'Neill R, Schickli J, Palese P, Henklein P, Bennink JR, Yewdell JW. 2001. A novel influenza A virus mitochondrial protein that induces cell death. Nature Medicine 7:1306-1312.
    14. Cheng W, Pan A, Rathbun SL, Ge Y, Xiao Q, Martinez L, Ling F, Liu S, Wang X, Yu Z, Ebell MH, Li C, Handel A, Chen E, Shen Y. 2021. Effectiveness of neuraminidase inhibitors to prevent mortality in patients with laboratory-confirmed avian influenza A H7N9. International Journal of Infectious Diseases 103:573-578.
    15. Chien CY, Xu Y, Xiao R, Aramini JM, Sahasrabudhe PV, Krug RM, Montelione GT. 2004. Biophysical characterization of the complex between double-stranded RNA and the N-terminal domain of the NS1 protein from influenza A virus: evidence for a novel RNA-binding mode. Biochemistry 43:1950-62.
    16. Dankar SK, Miranda E, Forbes NE, Pelchat M, Tavassoli A, Selman M, Ping J, Jia J, Brown EG. 2013. Influenza A/Hong Kong/156/1997(H5N1) virus NS1 gene mutations F103L and M106I both increase IFN antagonism, virulence and cytoplasmic localization but differ in binding to RIG-I and CPSF30. Virology Journal 10:243-265.
    17. 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. Proceedings of the National Academy of Sciences of the United States of America 105:13093-8.
    18. de Castro Martin IF, Fournier G, Sachse M, Pizarro-Cerda J, Risco C, Naffakh N. 2017. Influenza virus genome reaches the plasma membrane via a modified endoplasmic reticulum and Rab11-dependent vesicles. Nature Communication 8:1396-1407.
    19. DeDiego ML, Nogales A, Lambert-Emo K, Martinez-Sobrido L, Topham DJ. 2016. NS1 Protein Mutation I64T Affects Interferon Responses and Virulence of Circulating H3N2 Human Influenza A Viruses. Journal of Virology 90:9693-9711.
    20. Dharan NJ, Gubareva LV, Meyer JJ, Okomo-Adhiambo M, McClinton RC, Marshall SA, St. George K, Epperson S, Brammer L, Klimov AI, Bresee JS, Fry AM, Oseltamivir-Resistance Working Group ft. 2009. Infections With Oseltamivir-Resistant Influenza A(H1N1) Virus in the United States. JAMA 301:1034-1041.
    21. Dias A, Bouvier D, Crépin T, McCarthy AA, Hart DJ, Baudin F, Cusack S, Ruigrok RWH. 2009. The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit. Nature 458:914-918.
    22. Dortmans JC, Dekkers J, Wickramasinghe IN, Verheije MH, Rottier PJ, van Kuppeveld FJ, de Vries E, de Haan CA. 2013. Adaptation of novel H7N9 influenza A virus to human receptors. Scientific Reports 3:3058-64.
    23. Dou D, Revol R, Ostbye H, Wang H, Daniels R. 2018. Influenza A Virus Cell Entry, Replication, Virion Assembly and Movement. Frontiers in Immunology 9:1581-1597.
    24. Duan S, Govorkova EA, Bahl J, Zaraket H, Baranovich T, Seiler P, Prevost K, Webster RG, Webby RJ. 2014. Epistatic interactions between neuraminidase mutations facilitated the emergence of the oseltamivir-resistant H1N1 influenza viruses. Nature Communication 5:5029-5040.
    25. Dudek SE, Wixler L, Nordhoff C, Nordmann A, Anhlan D, Wixler V, Ludwig S. 2011. The influenza virus PB1-F2 protein has interferon antagonistic activity. Biological Chemistry 392:1135-44.
    26. Ehrhardt C, Wolff T, Pleschka S, Planz O, Beermann W, Bode JG, Schmolke M, Ludwig S. 2007. Influenza A virus NS1 protein activates the PI3K/Akt pathway to mediate antiapoptotic signaling responses. Journal of Virology 81:3058-67.
    27. Fan S, Deng G, Song J, Tian G, Suo Y, Jiang Y, Guan Y, Bu Z, Kawaoka Y, Chen H. 2009. Two amino acid residues in the matrix protein M1 contribute to the virulence difference of H5N1 avian influenza viruses in mice. Virology 384:28-32.
    28. Furuse Y, Suzuki A, Oshitani H. 2009. Large-scale sequence analysis of M gene of influenza A viruses from different species: mechanisms for emergence and spread of amantadine resistance. Antimicrobial Agents and Chemotherapy 53:4457-63.
    29. Hale BG, Steel J, Medina RA, Manicassamy B, Ye J, Hickman D, Hai R, Schmolke M, Lowen AC, Perez DR, Garcia-Sastre A. 2010. Inefficient control of host gene expression by the 2009 pandemic H1N1 influenza A virus NS1 protein. Journal of Virology 84:6909-22.
    30. Hayman A, Comely S, Lackenby A, Murphy S, McCauley J, Goodbourn S, Barclay W. 2006. Variation in the ability of human influenza A viruses to induce and inhibit the IFN-beta pathway. Virology 347:52-64.
    31. Hoffmann E, Neumann G, Kawaoka Y, Hobom G, Webster RG. 2000. A DNA transfection system for generation of influenza A virus from eight plasmids. Proceedings of the National Academy of Sciences of the United States of America 97:6108-13.
    32. Hung SJ, Hsu YM, Huang SW, Tsai HP, Lee LYY, Hurt AC, Barr IG, Shih SR, Wang JR. 2020. Genetic variations on 31 and 450 residues of influenza A nucleoprotein affect viral replication and translation. Journal of Biomedical Science 27:17-29.
    33. Hutchinson EC, Charles PD, Hester SS, Thomas B, Trudgian D, Martinez-Alonso M, Fodor E. 2015. Erratum: Conserved and host-specific features of influenza virion architecture. Nature Communication 6:6446-57.
    34. Ito T, Couceiro JN, Kelm S, Baum LG, Krauss S, Castrucci MR, Donatelli I, Kida H, Paulson JC, Webster RG, Kawaoka Y. 1998. Molecular basis for the generation in pigs of influenza A viruses with pandemic potential. Journal of Virology 72:7367-73.
    35. Iwasaki A, Pillai PS. 2014. Innate immunity to influenza virus infection. Nature Reviews: Immunology 14:315-28.
    36. 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 (PI3K). Virology 396:94-105.
    37. Kao LL. 2012. The effect of NS1 genetic variations of H3N2 influenza A virus on type I interferon. Master Thesis. National Cheng Kong University, Tainan, Taiwan.
    38. Keiner B, Maenz B, Wagner R, Cattoli G, Capua I, Klenk HD. 2010. Intracellular distribution of NS1 correlates with the infectivity and interferon antagonism of an avian influenza virus (H7N1). Journal of Virology 84:11858-65.
    39. Khandaker G, Zurynski Y, Buttery J, Marshall H, Richmond PC, Dale RC, Royle J, Gold M, Snelling T, Whitehead B, Jones C, Heron L, McCaskill M, Macartney K, Elliott EJ, Booy R. 2012. Neurologic complications of influenza A(H1N1)pdm09: surveillance in 6 pediatric hospitals. Neurology 79:1474-81.
    40. Khaperskyy DA, Schmaling S, Larkins-Ford J, McCormick C, Gaglia MM. 2016. Selective Degradation of Host RNA Polymerase II Transcripts by Influenza A Virus PA-X Host Shutoff Protein. PLoS Pathogens 12:e1005427-51.
    41. Kiefel MJ, von Itzstein M. 1999. Influenza virus sialidase: a target for drug discovery. Progress in Medicinal Chemistry 36:1-28.
    42. Kim HJ, Jeong MS, Jang SB. 2021. Structure and Activities of the NS1 Influenza Protein and Progress in the Development of Small-Molecule Drugs. International Journal of Molecular Sciences 22-33.
    43. Kleinpeter AB, Jureka AS, Falahat SM, Green TJ, Petit CM. 2018. Structural analyses reveal the mechanism of inhibition of influenza virus NS1 by two antiviral compounds. Journal of Biological Chemistry 293:14659-14668.
    44. Klemm C, Boergeling Y, Ludwig S, Ehrhardt C. 2018. Immunomodulatory Nonstructural Proteins of Influenza A Viruses. Trends in Microbiology 26:624-636.
    45. Kochs G, Garcia-Sastre A, Martinez-Sobrido L. 2007. Multiple anti-interferon actions of the influenza A virus NS1 protein. Journal of Virology 81:7011-21.
    46. Kochs G, Koerner I, Thiel L, Kothlow S, Kaspers B, Ruggli N, Summerfield A, Pavlovic J, Stech J, Staeheli P. 2007. Properties of H7N7 influenza A virus strain SC35M lacking interferon antagonist NS1 in mice and chickens. Journal of General Virology 88:1403-1409.
    47. Koliopoulos MG, Lethier M, van der Veen AG, Haubrich K, Hennig J, Kowalinski E, Stevens RV, Martin SR, Reis e Sousa C, Cusack S, Rittinger K. 2018. Molecular mechanism of influenza A NS1-mediated TRIM25 recognition and inhibition. Nature Communication 9:1820-1832.
    48. Korsun N, Angelova S, Trifonova I, Tzotcheva I, Mileva S, Voleva S, Georgieva I, Perenovska P. 2018. Predominance of influenza A(H3N2) viruses during the 2016/2017 season in Bulgaria. Journal of Medical Microbiology 67:228-239.
    49. Krammer F, Smith GJD, Fouchier RAM, Peiris M, Kedzierska K, Doherty PC, Palese P, Shaw ML, Treanor J, Webster RG, García-Sastre A. 2018. Influenza. Nature Reviews Disease Primers 4:3-23.
    50. Kratsch C, Klingen TR, Mumken L, Steinbruck L, McHardy AC. 2016. Determination of antigenicity-altering patches on the major surface protein of human influenza A/H3N2 viruses. Virus Evolution 2:vev025-036.
    51. Kuo RL, Krug RM. 2009. Influenza a virus polymerase is an integral component of the CPSF30-NS1A protein complex in infected cells. Journal of Virology 83:1611-6.
    52. Kwok KO, Riley S, Perera RAPM, Wei VWI, Wu P, Wei L, Chu DKW, Barr IG, Malik Peiris JS, Cowling BJ. 2017. Relative incidence and individual-level severity of seasonal influenza A H3N2 compared with 2009 pandemic H1N1. BMC Infectious Diseases 17:337-348.
    53. Lai S, Qin Y, Cowling BJ, Ren X, Wardrop NA, Gilbert M, Tsang TK, Wu P, Feng L, Jiang H, Peng Z, Zheng J, Liao Q, Li S, Horby PW, Farrar JJ, Gao GF, Tatem AJ, Yu H. 2016. Global epidemiology of avian influenza A H5N1 virus infection in humans, 1997-2015: a systematic review of individual case data. Lancet Infectious Diseases 16:e108-e118.
    54. Lee J, Yu H, Li Y, Ma J, Lang Y, Duff M, Henningson J, Liu Q, Li Y, Nagy A, Bawa B, Li Z, Tong G, Richt JA, Ma W. 2017. Impacts of different expressions of PA-X protein on 2009 pandemic H1N1 virus replication, pathogenicity and host immune responses. Virology 504:25-35.
    55. Li Y, Yamakita Y, Krug RM. 1998. Regulation of a nuclear export signal by an adjacent inhibitory sequence: the effector domain of the influenza virus NS1 protein. Proceedings of the National Academy of Sciences of the United States of America 95:4864-9.
    56. Litwack G. 2018. Chapter 10 - Nucleic Acids and Molecular Genetics, p 257-317. In Litwack G (ed), Human Biochemistry doi:https://doi.org/10.1016/B978-0-12-383864-3.00010-7. Academic Press, Boston.
    57. Liu STH, Behzadi MA, Sun W, Freyn AW, Liu WC, Broecker F, Albrecht RA, Bouvier NM, Simon V, Nachbagauer R, Krammer F, Palese P. 2018. Antigenic sites in influenza H1 hemagglutinin display species-specific immunodominance. Journal of Clinical Investigation 128:4992-4996.
    58. Livak KJ, Schmittgen TD. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25:402-8.
    59. Londt BZ, Brookes SM, Nash BJ, Nunez A, Stagg DA, Brown IH. 2013. The infectivity of pandemic 2009 H1N1 and avian influenza viruses for pigs: an assessment by ex vivo respiratory tract organ culture. Influenza and Other Respiratory Viruses 7:393-402.
    60. Lopes AM, Domingues P, Zell R, Hale BG. 2017. Structure-Guided Functional Annotation of the Influenza A Virus NS1 Protein Reveals Dynamic Evolution of the p85beta-Binding Site during Circulation in Humans. Journal of Virology 91:e01081-7.
    61. Malathi K, Dong B, Gale M, Jr., Silverman RH. 2007. Small self-RNA generated by RNase L amplifies antiviral innate immunity. Nature 448:816-9.
    62. Marc D. 2014. Influenza virus non-structural protein NS1: interferon antagonism and beyond. Journal of General Virology 95:2594-2611.
    63. 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. Proceedings of the National Academy of Sciences of the United States of America 103:7100-5.
    64. Mitra S, Kumar D, Hu L, Sankaran B, Moosa MM, Rice AP, Ferreon JC, Ferreon ACM, Prasad BVV. 2019. Influenza A Virus Protein NS1 Exhibits Strain-Independent Conformational Plasticity. Journal of Virology 93 :e00917-19.
    65. Noah DL, Twu KY, Krug RM. 2003. Cellular antiviral responses against influenza A virus are countered at the posttranscriptional level by the viral NS1A protein via its binding to a cellular protein required for the 3' end processing of cellular pre-mRNAS. Virology 307:386-95.
    66. Novel Swine-Origin Influenza AVIT, 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. New England Journal of Medicine 360:2605-15.
    67. Obenauer JC, Denson J, Mehta PK, Su X, Mukatira S, Finkelstein DB, Xu X, Wang J, Ma J, Fan Y, Rakestraw KM, Webster RG, Hoffmann E, Krauss S, Zheng J, Zhang Z, Naeve CW. 2006. Large-scale sequence analysis of avian influenza isolates. Science 311:1576-80.
    68. Panthu B, Terrier O, Carron C, Traversier A, Corbin A, Balvay L, Lina B, Rosa-Calatrava M, Ohlmann T. 2017. The NS1 Protein from Influenza Virus Stimulates Translation Initiation by Enhancing Ribosome Recruitment to mRNAs. Journal of Molecular Biology 429:3334-3352.
    69. Pauly MD, Procario MC, Lauring AS. 2017. A novel twelve class fluctuation test reveals higher than expected mutation rates for influenza A viruses. Elife 6.
    70. Petrova VN, Russell CA. 2018. The evolution of seasonal influenza viruses. Nature Reviews Microbiology 16:47-60.
    71. Potter BI, Kondor R, Hadfield J, Huddleston J, Barnes J, Rowe T, Guo L, Xu X, Neher RA, Bedford T, Wentworth DE. 2019. Evolution and rapid spread of a reassortant A(H3N2) virus that predominated the 2017-2018 influenza season. Virus Evolution 5:vez046-052.
    72. Robb NC, Chase G, Bier K, Vreede FT, Shaw PC, Naffakh N, Schwemmle M, Fodor E. 2011. The influenza A virus NS1 protein interacts with the nucleoprotein of viral ribonucleoprotein complexes. Journal of Virology 85:5228-31.
    73. Rossman JS, Lamb RA. 2011. Influenza virus assembly and budding. Virology 411:229-36.
    74. Sadler AJ, Williams BR. 2008. Interferon-inducible antiviral effectors. Nature Reviews: Immunology 8:559-68.
    75. Simon B, Pichon M, Valette M, Burfin G, Richard M, Lina B, Josset L. 2019. Whole Genome Sequencing of A(H3N2) Influenza Viruses Reveals Variants Associated with Severity during the 2016(-)2017 Season. Viruses 11:108-122.
    76. Soh YS, Moncla LH, Eguia R, Bedford T, Bloom JD. 2019. Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans. Elife 8 :e45079-45106.
    77. Stray SJ, Pittman LB. 2012. Subtype- and antigenic site-specific differences in biophysical influences on evolution of influenza virus hemagglutinin. Virology Journal 9:91-106.
    78. Tawaratsumida K, Phan V, Hrincius ER, High AA, Webby R, Redecke V, Hacker H. 2014. Quantitative proteomic analysis of the influenza A virus nonstructural proteins NS1 and NS2 during natural cell infection identifies PACT as an NS1 target protein and antiviral host factor. Journal of Virology 88:9038-48.
    79. Tscherne DM, Garcia-Sastre A. 2011. Virulence determinants of pandemic influenza viruses. Journal of Clinical Investigation 121:6-13.
    80. Tsou TP, Su CP, Huang WT, Yang JR, Liu MT. 2017. Influenza A(H3N2) virus variants and patient characteristics during a summer influenza epidemic in Taiwan, 2017. Euro Surveillance 22 (50):pii=17-00767.
    81. Tu J, Guo J, Zhang A, Zhang W, Zhao Z, Zhou H, Liu C, Chen H, Jin M. 2011. Effects of the C-terminal truncation in NS1 protein of the 2009 pandemic H1N1 influenza virus on host gene expression. PloS One 6:e26175-82.
    82. Twu KY, Kuo RL, Marklund J, Krug RM. 2007. The H5N1 influenza virus NS genes selected after 1998 enhance virus replication in mammalian cells. Journal of Virology 81:8112-21.
    83. Tynell J, Melen K, Julkunen I. 2014. Mutations within the conserved NS1 nuclear export signal lead to inhibition of influenza A virus replication. Virology Journal 11:128-139.
    84. Wendel I, Matrosovich M, Klenk HD. 2015. SnapShot: Evolution of human influenza A viruses. Cell Host & Microbe 17:416-416 e1.
    85. World Health Organization. 6 November 2018. Influenza (Seasonal) Available from: https://www.who.int/en/news-room/fact-sheets/detail/influenza-(seasonal).
    86. Wu WWH, Weaver LL, Panté N. 2007. Ultrastructural Analysis of the Nuclear Localization Sequences on Influenza A Ribonucleoprotein Complexes. Journal of Molecular Biology 374:910-916.
    87. Yamada S, Hatta M, Staker BL, Watanabe S, Imai M, Shinya K, Sakai-Tagawa Y, Ito M, Ozawa M, Watanabe T, Sakabe S, Li C, Kim JH, Myler PJ, Phan I, Raymond A, Smith E, Stacy R, Nidom CA, Lank SM, Wiseman RW, Bimber BN, O'Connor DH, Neumann G, Stewart LJ, Kawaoka Y. 2010. Biological and structural characterization of a host-adapting amino acid in influenza virus. PLoS Pathogens 6:e1001034-44.
    88. Yang JR, Kuo CY, Huang HY, Hsu SZ, Wu FT, Wu FT, Li CH, Liu MT. 2020. Seasonal dynamics of influenza viruses and age distribution of infected individuals across nine seasons covering 2009-2018 in Taiwan. Journal of the Formosan Medical Association 119:850-860.
    89. York A, Fodor E. 2013. Biogenesis, assembly, and export of viral messenger ribonucleoproteins in the influenza A virus infected cell. RNA Biology 10:1274-1282.
    90. Zhang K, Xie Y, Munoz-Moreno R, Wang J, Zhang L, Esparza M, Garcia-Sastre A, Fontoura BMA, Ren Y. 2019. Structural basis for influenza virus NS1 protein block of mRNA nuclear export. Nature Microbiology 4:1671-1679.
    91. Zheng H, Lee HA, Palese P, García-Sastre A. 1999. Influenza A virus RNA polymerase has the ability to stutter at the polyadenylation site of a viral RNA template during RNA replication. Journal of Virology 73:5240-5243.
    92. Zost SJ, Parkhouse K, Gumina ME, Kim K, Diaz Perez S, Wilson PC, Treanor JJ, Sant AJ, Cobey S, Hensley SE. 2017. Contemporary H3N2 influenza viruses have a glycosylation site that alters binding of antibodies elicited by egg-adapted vaccine strains. Proceedings of the National Academy of Sciences 114:12578-12583.

    無法下載圖示 校內：2026-10-18公開
    校外：2026-10-18公開
    電子論文尚未授權公開，紙本請查館藏目錄
    QR CODE