Influenza virus polymerase: Functions on host range, inhibition of cellular response to infection and pathogenicity

Virus Research

Volumn 209, Issue , 2015, Pages 23-38

  Rodriguez Frandsen, Ariel ^a,b,c   Alfonso, Roberto ^a,b,d   Nieto, Amelia ^a,b  

^a CENTRO NACIONAL DE BIOTECNOLOGÍA   (Spain)

^b INSTITUTO DE SALUD CARLOS III   (Spain)

^c BURNHAM INSTITUTE   (United States)

^d NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

Author keywords

Host adaptation; Influenza virus; Pathogenicity; RNA polymerase II; Viral polymerase; Virulence

Indexed keywords

CELL PROTEIN; HOST FACTOR; N40 PROTEIN; NONSTRUCTURAL PROTEIN 1; PA DERIVED PROTEIN; PB1 F2 PROTEIN; PROTEOME; RNA DIRECTED RNA POLYMERASE; RNA POLYMERASE II; TRANSCRIPTOME; UNCLASSIFIED DRUG; VIRULENCE FACTOR; VIRUS ENZYME; VIRUS PROTEIN; VIRUS RNA; DNA DIRECTED RNA POLYMERASE; MUTANT PROTEIN;

2009 H1N1 INFLUENZA; ADAPTATION; AMINO TERMINAL SEQUENCE; AVIAN INFLUENZA (H5N1); CARBOXY TERMINAL SEQUENCE; CELLULAR IMMUNITY; ENZYME POLYMORPHISM; GENE EXPRESSION; GENETIC REASSORTMENT; GENETIC VARIABILITY; HOST RANGE; HUMAN; INFLUENZA A; INFLUENZA A (H5N1); INFLUENZA A VIRUS; INFLUENZA A VIRUS (H1N1); INFLUENZA A VIRUS (H3N2); INFLUENZA A VIRUS (H3N8); INFLUENZA A VIRUS (H5N1); INFLUENZA A VIRUS (H7N7); INFLUENZA A VIRUS (H7N9); INFLUENZA A VIRUS (H9N2); NONHUMAN; NONSENSE MUTATION; OPEN READING FRAME; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN DEGRADATION; PROTEIN EXPRESSION; REVIEW; RNA TRANSLATION; VIRUS CELL INTERACTION; VIRUS REPLICATION; VIRUS STRAIN; VIRUS TRANSMISSION; VIRUS VIRULENCE; ANIMAL; ENZYMOLOGY; GENETICS; HOST PATHOGEN INTERACTION; IMMUNE EVASION; METABOLISM; ORTHOMYXOVIRIDAE; PATHOGENICITY; PHYSIOLOGY; VIRULENCE;

ADAPTATION, BIOLOGICAL; ANIMALS; DNA-DIRECTED RNA POLYMERASES; HOST SPECIFICITY; HOST-PATHOGEN INTERACTIONS; HUMANS; IMMUNE EVASION; MUTANT PROTEINS; ORTHOMYXOVIRIDAE; VIRULENCE; VIRUS REPLICATION;

EID: 84958556848     PISSN: 01681702     EISSN: 18727492     Source Type: Journal    
DOI: 10.1016/j.virusres.2015.03.017     Document Type: Review

References (215)

1. Akkina R.K., Richardson J.C., Aguilera M.C., Yang C.M. Heterogeneous forms of polymerase proteins exist in influenza A virus-infected cells. Virus Res. 1991, 19(1):17-30.
2. Alfonso R., Lutz T., Rodriguez A., Chavez J.P., Rodriguez P., Gutierrez S., Nieto A. CHD6 chromatin remodeler is a negative modulator of influenza virus replication that relocates to inactive chromatin upon infection. Cell. Microbiol. 2011, 13(12):1894-1906.
3. Alfonso R., Rodriguez A., Rodriguez P., Lutz T., Nieto A. CHD6, a cellular repressor of influenza virus replication, is degraded in human alveolar epithelial cells and mice lungs during infection. J. Virol. 2013, 87(8):4534-4544.
4. Almond J.W. A single gene determines the host range of influenza virus. Nature 1977, 270(5638):617-618.
5. Alymova I.V., Green A.M., van de Velde N., McAuley J.L., Boyd K.L., Ghoneim H.E., McCullers J.A. Immunopathogenic and antibacterial effects of H3N2 influenza A virus PB1-F2 map to amino acid residues 62, 75, 79, and 82. J. Virol. 2011, 85(23):12324-12333.
6. Alymova I.V., Samarasinghe A., Vogel P., Green A.M., Weinlich R., McCullers J.A. A novel cytotoxic sequence contributes to influenza A viral protein PB1-F2 pathogenicity and predisposition to secondary bacterial infection. J. Virol. 2014, 88(1):503-515.
7. Antonopoulou A., Baziaka F., Tsaganos T., Raftogiannis M., Koutoukas P., Spyridaki A., Mouktaroudi M., Kotsaki A., Savva A., Georgitsi M., Giamarellos-Bourboulis E.J. Role of tumor necrosis factor gene single nucleotide polymorphisms in the natural course of 2009 influenza A H1N1 virus infection. Int. J. Infect. Dis.: IJID: Off. Publ. Int. Soc. Infect. Dis. 2012, 16(3):e204-e208.
8. Area E., Martin-Benito J., Gastaminza P., Torreira E., Valpuesta J.M., Carrascosa J.L., Ortin J. 3D structure of the influenza virus polymerase complex: localization of subunit domains. Proc. Natl. Acad. Sci. U.S.A. 2004, 101(1):308-313.
9. Arranz R., Coloma R., Chichon F.J., Conesa J.J., Carrascosa J.L., Valpuesta J.M., Ortin J., Martin-Benito J. The structure of native influenza virion ribonucleoproteins. Science 2012, 338(6114):1634-1637.
10. Beloso A., Martinez C., Valcarcel J., Santaren J.F., Ortin J. Degradation of cellular mRNA during influenza virus infection: its possible role in protein synthesis shutoff. J. Gen. Virol. 1992, 73(Pt 3):575-581.
11. Blaas D., Patzelt E., Kuechler E. Identification of the cap binding protein of influenza virus. Nucl. Acids Res. 1982, 10(15):4803-4812.
12. Bogs J., Kalthoff D., Veits J., Pavlova S., Schwemmle M., Manz B., Mettenleiter T.C., Stech J. Reversion of PB2-627E to -627 K during replication of an H5N1 Clade 2.2 virus in mammalian hosts depends on the origin of the nucleoprotein. J. Virol. 2011, 85(20):10691-10698.
13. Bortz E., Westera L., Maamary J., Steel J., Albrecht R.A., Manicassamy B., Chase G., Martinez-Sobrido L., Schwemmle M., Garcia-Sastre A. Host- and strain-specific regulation of influenza virus polymerase activity by interacting cellular proteins. mBio 2011, 2(4).
14. Braam J., Ulmanen I., Krug R.M. Molecular model of a eucaryotic transcription complex: functions and movements of influenza P proteins during capped RNA-primed transcription. Cell 1983, 34(2):609-618.
15. Bradel-Tretheway B.G., Mattiacio J.L., Krasnoselsky A., Stevenson C., Purdy D., Dewhurst S., Katze M.G. Comprehensive proteomic analysis of influenza virus polymerase complex reveals a novel association with mitochondrial proteins and RNA polymerase accessory factors. J. Virol. 2011, 85(17):8569-8581.
16. Brass A.L., Huang I.C., Benita Y., John S.P., Krishnan M.N., Feeley E.M., Ryan B.J., Weyer J.L., van der Weyden L., Fikrig E., Adams D.J., Xavier R.J., Farzan M., Elledge S.J. The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. Cell 2009, 139(7):1243-1254.
17. Brown E.G., Liu H., Kit L.C., Baird S., Nesrallah M. Pattern of mutation in the genome of influenza A virus on adaptation to increased virulence in the mouse lung: identification of functional themes. Proc. Natl. Acad. Sci. U.S.A. 2001, 98(12):6883-6888.
18. Burgui I., Yángüez E., Sonenberg N., Nieto A. Influenza virus mRNA translation revisited: is the eIF4E cap-binding factor required for viral mRNA translation?. Virology 2007, 81(November (22)):12427-12438.
19. Bussey K.A., Desmet E.A., Mattiacio J.L., Hamilton A., Bradel-Tretheway B., Bussey H.E., Kim B., Dewhurst S., Takimoto T. PA residues in the 2009 H1N1 pandemic influenza virus enhance avian influenza virus polymerase activity in mammalian cells. J. Virol. 2011, 85(14):7020-7028.
20. Carr S.M., Carnero E., Garcia-Sastre A., Brownlee G.G., Fodor E. Characterization of a mitochondrial-targeting signal in the PB2 protein of influenza viruses. Virology 2006, 344(2):492-508.
21. Coloma R., Valpuesta J.M., Arranz R., Carrascosa J.L., Ortin J., Martin-Benito J. The structure of a biologically active influenza virus ribonucleoprotein complex. PLoS Pathog. 2009, 5(6):e1000491.
22. Conenello G.M., Tisoncik J.R., Rosenzweig E., Varga Z.T., Palese P., Katze M.G. A single N66S mutation in the PB1-F2 protein of influenza A virus increases virulence by inhibiting the early interferon response in vivo. J. Virol. 2011, 85(2):652-662.
23. Conenello G.M., Zamarin D., Perrone L.A., 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):1414-1421.
24. Czudai-Matwich V., Otte A., Matrosovich M., Gabriel G., Klenk H.D. PB2 Mutations D701 N and S714R Promote Adaptation of an Influenza H5N1 Virus to a Mammalian Host. J. Virol. 2014, 88(16):8735-8742.
25. Chan A.Y., Vreede F.T., Smith M., Engelhardt O.G., Fodor E. Influenza virus inhibits RNA polymerase II elongation. Virology 2006, 351(1):210-217.
26. Chanturiya A.N., Basanez G., Schubert U., Henklein P., Yewdell J.W., Zimmerberg J. PB1-F2, an influenza A virus-encoded proapoptotic mitochondrial protein, creates variably sized pores in planar lipid membranes. J. Virol. 2004, 78(12):6304-6312.
27. Chase G.P., Rameix-Welti M.A., Zvirbliene A., Zvirblis G., Gotz V., Wolff T., Naffakh N., Schwemmle M. Influenza virus ribonucleoprotein complexes gain preferential access to cellular export machinery through chromatin targeting. PLoS Pathog. 2011, 7(9):e1002187.
28. Chen G., Liu C.H., Zhou L., Krug R.M. Cellular DDX21 RNA helicase inhibits influenza A virus replication but is counteracted by the viral NS1 protein. Cell Host Microbe 2014, 15(4):484-493.
29. Chen W., Calvo P.A., Malide D., Gibbs J., Schubert U., Bacik I., Basta S., O'Neill R., Schickli J., Palese P., Henklein P., Bennink J.R., Yewdell J.W. A novel influenza A virus mitochondrial protein that induces cell death. Nature Med. 2001, 7(12):1306-1312.
30. de Graaf M., Fouchier R.A. Role of receptor binding specificity in influenza A virus transmission and pathogenesis. EMBO J. 2014, 33(8):823-841.
31. de Jong M.D., Simmons C.P., Thanh T.T., Hien V.M., Smith G.J., Chau T.N., Hoang D.M., Chau N.V., Khanh T.H., Dong V.C., Qui P.T., Cam B.V., Ha do Q., Guan Y., Peiris J.S., Chinh N.T., Hien T.T., Farrar J. Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nature Med. 2006, 12(10):1203-1207.
32. de Jong R.M., Stockhofe-Zurwieden N., Verheij E.S., de Boer-Luijtze E.A., Ruiter S.J., de Leeuw O.S., Cornelissen L.A. Rapid emergence of a virulent PB2 E627 K variant during adaptation of highly pathogenic avian influenza H7N7 virus to mice. Virol. J. 2013, 10:276.
33. Deng T., Engelhardt O.G., Thomas B., Akoulitchev A.V., Brownlee G.G., Fodor E. Role of ran binding protein 5 in nuclear import and assembly of the influenza virus RNA polymerase complex. J. Virol. 2006, 80(24):11911-11919.
34. Desmet E.A., Bussey K.A., Stone R., Takimoto T. Identification of the N-terminal domain of the influenza virus PA responsible for the suppression of host protein synthesis. J. Virol. 2013, 87(6):3108-3118.
35. Dias A., Bouvier D., Crepin T., McCarthy A.A., Hart D.J., Baudin F., Cusack S., Ruigrok R.W. The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit. Nature 2009, 458(7240):914-918.
36. Dudek S.E., Wixler L., Nordhoff C., Nordmann A., Anhlan D., Wixler V., Ludwig S. The influenza virus PB1-F2 protein has interferon antagonistic activity. Biolog. Chem. 2011, 392(12):1135-1144.
37. Engelhardt O.G., Smith M., Fodor E. Association of the influenza A virus RNA-dependent RNA polymerase with cellular RNA polymerase II. J. Virol. 2005, 79(9):5812-5818.
38. Everitt A.R., Clare S., Pertel T., John S.P., Wash R.S., Smith S.E., Chin C.R., Feeley E.M., Sims J.S., Adams D.J., Wise H.M., Kane L., Goulding D., Digard P., Anttila V., Baillie J.K., Walsh T.S., Hume D.A., Palotie A., Xue Y., Colonna V., Tyler-Smith C., Dunning J., Gordon S.B., Gen I.I., Investigators M., Smyth R.L., Openshaw P.J., Dougan G., Brass A.L., Kellam P. IFITM3 restricts the morbidity and mortality associated with influenza. Nature 2012, 484(7395):519-523.
39. Firth A.E., Jagger B.W., Wise H.M., Nelson C.C., Parsawar K., Wills N.M., Napthine S., Taubenberger J.K., Digard P., Atkins J.F. Ribosomal frameshifting used in influenza A virus expression occurs within the sequence UCC_UUU_CGU and is in the +1 direction. Open Biol. 2012, 2(10):120109.
40. Florent G. Gene constellation of live influenza A vaccines. Arch. Virol. 1980, 64(2):171-173.
41. Fodor E. The RNA polymerase of influenza a virus: mechanisms of viral transcription and replication. Acta Virolog. 2013, 57(2):113-122.
42. Foeglein A., Loucaides E.M., Mura M., Wise H.M., Barclay W.S., Digard P. Influence of PB2 host-range determinants on the intranuclear mobility of the influenza A virus polymerase. J. Gen. Virol. 2011, 92(Pt 7):1650-1661.
43. Fortes P., Beloso A., Ortin J. Influenza virus NS1 protein inhibits pre-mRNA splicing and blocks mRNA nucleocytoplasmic transport. EMBO J. 1994, 13(3):704-712.
44. Fortes P., Lamond A.I., Ortin J. Influenza virus NS1 protein alters the subnuclear localization of cellular splicing components. J. Gen. Virol. 1995, 76(Pt 4):1001-1007.
45. Fouchier R.A., Schneeberger P.M., Rozendaal F.W., Broekman J.M., Kemink S.A., Munster V., Kuiken T., Rimmelzwaan G.F., Schutten M., Van Doornum G.J., Koch G., Bosman A., Koopmans M., Osterhaus A.D. 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. 2004, 101(5):1356-1361.
46. Fournier G., Chiang C., Munier S., Tomoiu A., Demeret C., Vidalain P.O., Jacob Y., Naffakh N. Recruitment of RED-SMU1 complex by Influenza A Virus RNA polymerase to control Ciral mRNA splicing. PLoS Pathog. 2014, 10(6):e1004164.
47. Gabriel G., Dauber B., Wolff T., Planz O., Klenk H.D., Stech J. The viral polymerase mediates adaptation of an avian influenza virus to a mammalian host. Proc. Natl. Acad. Sci. U.S.A. 2005, 102(51):18590-18595.
48. Gabriel G., Klingel K., Otte A., Thiele S., Hudjetz B., Arman-Kalcek G., Sauter M., Shmidt T., Rother F., Baumgarte S., Keiner B., Hartmann E., Bader M., Brownlee G.G., Fodor E., Klenk H.D. Differential use of importin-alpha isoforms governs cell tropism and host adaptation of influenza virus. Nature Commun. 2011, 2:156.
49. Gack M.U., Albrecht R.A., Urano T., Inn K.S., Huang I.C., Carnero E., Farzan M., Inoue S., Jung J.U., Garcia-Sastre A. Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I. Cell Host Microbe 2009, 5(5):439-449.
50. Gao P., Watanabe S., Ito T., Goto H., Wells K., McGregor M., Cooley A.J., Kawaoka Y. Biological heterogeneity, including systemic replication in mice, of H5N1 influenza A virus isolates from humans in Hong Kong. J. Virol. 1999, 73(4):3184-3189.
51. Gao Y., Zhang Y., Shinya K., Deng G., Jiang Y., Li Z., Guan Y., Tian G., Li Y., Shi J., Liu L., Zeng X., Bu Z., Xia X., Kawaoka Y., Chen H. 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.
52. Garcia-Robles I., Akarsu H., Muller C.W., Ruigrok R.W., Baudin F. Interaction of influenza virus proteins with nucleosomes. Virology 2005, 332(1):329-336.
53. Garfinkel M.S., Katze M.G. Translational control by influenza virus. Selective translation is mediated by sequences within the viral mRNA 5'-untranslated region. J. Biol. Chem. 1993, 268(30):22223-22226.
54. Gibbs J.S., Malide D., Hornung F., Bennink J.R., Yewdell J.W. The influenza A virus PB1-F2 protein targets the inner mitochondrial membrane via a predicted basic amphipathic helix that disrupts mitochondrial function. J. Virol. 2003, 77(13):7214-7224.
55. Graef K.M., Vreede F.T., Lau Y.F., McCall A.W., Carr S.M., Subbarao K., Fodor E. The PB2 subunit of the influenza virus RNA polymerase affects virulence by interacting with the mitochondrial antiviral signaling protein and inhibiting expression of beta interferon. J. Virol. 2010, 84(17):8433-8445.
56. Grimm, D., Staeheli, P., Hufbauer, M., Koerner, I., Martinez-Sobrido, L., Solorzano, A., Garcia-Sastre, A., Haller, O., Kochs, G., 2007. Replication fitness determines high virulence of influenza A virus in mice carrying functional Mx1 resistance gene. Proc. Natl. Acad. Sci. U.S.A. 104(16), 6806-6811.
57. Guilligay D., Tarendeau F., Resa-Infante P., Coloma R., Crepin T., Sehr P., Lewis J., Ruigrok R.W., Ortin J., Hart D.J., Cusack S. The structural basis for cap binding by influenza virus polymerase subunit PB2. Nature Struct. Mol. Biol. 2008, 15(5):500-506.
58. Hai R., Schmolke M., Varga Z.T., Manicassamy B., Wang T.T., Belser J.A., Pearce M.B., Garcia-Sastre A., Tumpey T.M., Palese P. PB1-F2 expression by the 2009 pandemic H1N1 influenza virus has minimal impact on virulence in animal models. J. Virol. 2010, 84(9):4442-4450.
59. Hao L., Sakurai A., Watanabe T., Sorensen E., Nidom C.A., Newton M.A., Ahlquist P., Kawaoka Y. Drosophila RNAi screen identifies host genes important for influenza virus replication. Nature 2008, 454(7206):890-893.
60. Hatta M., Gao P., Halfmann P., Kawaoka Y. Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science 2001, 293(5536):1840-1842.
61. Hatta M., Hatta Y., Kim J.H., Watanabe S., Shinya K., Nguyen T., Lien P.S., Le Q.M., Kawaoka Y. Growth of H5N1 influenza A viruses in the upper respiratory tracts of mice. PLoS Pathog. 2007, 3(10):1374-1379.
62. Hay A.J., Lomniczi B., Bellamy A.R., Skehel J.J. Transcription of the influenza virus genome. Virology 1977, 83(2):337-355.
63. He X., Zhou J., Bartlam M., Zhang R., Ma J., Lou Z., Li X., Li J., Joachimiak A., Zeng Z., Ge R., Rao Z., Liu Y. Crystal structure of the polymerase PA(C)-PB1(N) complex from an avian influenza H5N1 virus. Nature 2008, 454(7208):1123-1126.
64. Herfst S., Chutinimitkul S., Ye J., de Wit E., Munster V.J., Schrauwen E.J., Bestebroer T.M., Jonges M., Meijer A., Koopmans M., Rimmelzwaan G.F., Osterhaus A.D., Perez D.R., Fouchier R.A. Introduction of virulence markers in PB2 of pandemic swine-origin influenza virus does not result in enhanced virulence or transmission. J. Virol. 2010, 84(8):3752-3758.
65. Herfst S., Schrauwen E.J., Linster M., Chutinimitkul S., de Wit E., Munster V.J., Sorrell E.M., Bestebroer T.M., Burke D.F., Smith D.J., Rimmelzwaan G.F., Osterhaus A.D., Fouchier R.A. Airborne transmission of influenza A/H5N1 virus between ferrets. Science 2012, 336(6088):1534-1541.
66. Herlocher M.L., Clavo A.C., Maassab H.F. Sequence comparisons of A/AA/6/60 influenza viruses: mutations which may contribute to attenuation. Virus Res. 1996, 42(1-2):11-25.
67. Hiromoto Y., Saito T., Lindstrom S., Nerome K. Characterization of low virulent strains of highly pathogenic A/Hong Kong/156/97 (H5N1) virus in mice after passage in embryonated hens' eggs. Virology 2000, 272(2):429-437.
68. Hsu W.B., Shih J.L., Shih J.R., Du J.L., Teng S.C., Huang L.M., Wang W.B. Cellular protein HAX1 interacts with the influenza A virus PA polymerase subunit and impedes its nuclear translocation. J. Virol. 2013, 87(1):110-123.
69. Hu J., Liu X. Crucial Role of PA in Virus Life Cycle and Host Adaptation of Influenza A Virus 2014, Medical Microbiology and Immunology.
70. Huarte M., Falcon A., Nakaya Y., Ortin J., Garcia-Sastre A., Nieto A. Threonine 157 of influenza virus PA polymerase subunit modulates RNA replication in infectious viruses. J. Virol. 2003, 77(10):6007-6013.
71. Huarte M., Sanz-Ezquerro J.J., Roncal F., Ortin J., Nieto A. PA subunit from influenza virus polymerase complex interacts with a cellular protein with homology to a family of transcriptional activators. J. Virol. 2001, 75(18):8597-8604.
72. Hudjetz B., Gabriel G. Human-like PB2 627K influenza virus polymerase activity is regulated by importin-alpha1 and -alpha7. PLoS Pathog. 2012, 8(1):e1002488.
73. Ilyushina N.A., Khalenkov A.M., Seiler J.P., Forrest H.L., Bovin N.V., Marjuki H., Barman S., Webster R.G., Webby R.J. Adaptation of pandemic H1N1 influenza viruses in mice. J. Virol. 2010, 84(17):8607-8616.
74. Inglis S.C. Inhibition of host protein synthesis and degradation of cellular mRNAs during infection by influenza and herpes simplex virus. Mol. Cell. Biol. 1982, 2(12):1644-1648.
75. Isakova-Sivak I., Chen L.M., Matsuoka Y., Voeten J.T., Kiseleva I., Heldens J.G., den Bosch H., Klimov A., Rudenko L., Cox N.J., Donis R.O. Genetic bases of the temperature-sensitive phenotype of a master donor virus used in live attenuated influenza vaccines: A/Leningrad/134/17/57 (H2N2). Virology 2011, 412(2):297-305.
76. Iwasaki A., Pillai P.S. Innate immunity to influenza virus infection. Nature reviews. Immunology 2014, 14(5):315-328.
77. Jagger B.W., Memoli M.J., Sheng Z.M., Qi L., Hrabal R.J., Allen G.L., Dugan V.G., Wang R., Digard P., Kash J.C., Taubenberger J.K. The PB2-E627 K mutation attenuates viruses containing the 2009 H1N1 influenza pandemic polymerase. mBio 2010, 1(1).
78. Jagger B.W., Wise H.M., Kash J.C., Walters K.A., Wills N.M., Xiao Y.L., Dunfee R.L., Schwartzman L.M., Ozinsky A., Bell G.L., Dalton R.M., Lo A., Efstathiou S., Atkins J.F., Firth A.E., Taubenberger J.K., Digard P. An overlapping protein-coding region in influenza A virus segment 3 modulates the host response. Science 2012, 337(6091):199-204.
79. Johnson N.P., Mueller J. Updating the accounts: global mortality of the 1918-1920 Spanish influenza pandemic. Bull. History Med. 2002, 76(1):105-115.
80. Jorba N., Coloma R., Ortin J. Genetic trans-complementation establishes a new model for influenza virus RNA transcription and replication. PLoS Pathog. 2009, 5(5):e1000462.
81. Jorba N., Juarez S., Torreira E., Gastaminza P., Zamarreno N., Albar J.P., Ortin J. Analysis of the interaction of influenza virus polymerase complex with human cell factors. Proteomics 2008, 8(10):2077-2088.
82. Kageyama T., Fujisaki S., Takashita E., Xu H., Yamada S., Uchida Y., Neumann G., Saito T., Kawaoka Y., Tashiro M. Genetic analysis of novel avian A(H7N9) influenza viruses isolated from patients in China, February to April 2013. Euro surveillance: bulletin Europeen sur les maladies transmissibles. Euro. Commun. Dis. Bull. 2013, 18(15):20453.
83. Kakugawa S., Shimojima M., Neumann G., Goto H., Kawaoka Y. RuvB-like protein 2 is a suppressor of influenza A virus polymerases. J. Virol. 2009, 83(13):6429-6434.
84. Karlas A., Machuy N., Shin Y., Pleissner K.P., Artarini A., Heuer D., Becker D., Khalil H., Ogilvie L.A., Hess S., Maurer A.P., Muller E., Wolff T., Rudel T., Meyer T.F. Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication. Nature 2010, 463(7282):818-822.
85. Kashiwagi T., Leung B.W., Deng T., Chen H., Brownlee G.G. The N-terminal region of the PA subunit of the RNA polymerase of influenza A/HongKong/156/97 (H5N1) influences promoter binding. PloS One 2009, 4(5):e5473.
86. Kawaguchi A., Nagata K. De novo replication of the influenza virus RNA genome is regulated by DNA replicative helicase, MCM. EMBO J. 2007, 26(21):4566-4575.
87. Kawaoka Y., Krauss S., Webster R.G. Avian-to-human transmission of the PB1 gene of influenza A viruses in the 1957 and 1968 pandemics. J. Virol. 1989, 63(11):4603-4608.
88. Keynan Y., Juno J., Meyers A., Ball T.B., Kumar A., Rubinstein E., Fowke K.R. Chemokine receptor 5 big up tri, open32 allele in patients with severe pandemic (H1N1) 2009. Emerg. Infect. Dis. 2010, 16(10):1621-1622.
89. Khaperskyy D.A., Emara M.M., Johnston B.P., Anderson P., Hatchette T.F., McCormick C. Influenza a virus host shutoff disables antiviral stress-induced translation arrest. PLoS Pathog. 2014, 10(7):e1004217.
90. Kim J.H., Hatta M., Watanabe S., Neumann G., Watanabe T., Kawaoka Y. Role of host-specific amino acids in the pathogenicity of avian H5N1 influenza viruses in mice. J. Gen. Virol. 2010, 91(Pt 5):1284-1289.
91. Klimov A., Kiseleva I., Alexandrova G., Cox N. Genes coding for polymerase proteins are essential for attenuation of the cold-adapted A/Leningrad/134/17/57 (H2N2) influenza virus. Int. Congress Ser. 2001, 1219:955-959.
92. Klimov A.I., Cox N.J., Yotov W.V., Rocha E., Alexandrova G.I., Kendal A.P. Sequence changes in the live attenuated, cold-adapted variants of influenza A/Leningrad/134/57 (H2N2) virus. Virology 1992, 186(2):795-797.
93. Knipe D.M., Lieberman P.M., Jung J.U., McBride A.A., Morris K.V., Ott M., Margolis D., Nieto A., Nevels M., Parks R.J., Kristie T.M. Snapshots: chromatin control of viral infection. Virology 2013, 435(1):141-156.
94. Kobayashi M., Toyoda T., Ishihama A. Influenza virus PB1 protein is the minimal and essential subunit of RNA polymerase. Arch. Virol. 1996, 141(3-4):525-539.
95. Konig R., Stertz S., Zhou Y., Inoue A., Hoffmann H.H., Bhattacharyya S., Alamares J.G., Tscherne D.M., Ortigoza M.B., Liang Y., Gao Q., Andrews S.E., Bandyopadhyay S., De Jesus P., Tu B.P., Pache L., Shih C., Orth A., Bonamy G., Miraglia L., Ideker T., Garcia-Sastre A., Young J.A., Palese P., Shaw M.L., Chanda S.K. Human host factors required for influenza virus replication. Nature 2010, 463(7282):813-817.
96. Kosik I., Krejnusova I., Bystricka M., Polakova K., Russ G. N-terminal region of the PB1-F2 protein is responsible for increased expression of influenza A viral protein PB1. Acta Virol. 2011, 55(1):45-53.
97. Krug R.M., Broni B.A., Bouloy M. Are the 5' ends of influenza viral mRNAs synthesized in vivo donated by host mRNAs?. Cell 1979, 18(2):329-334.
98. Kuzuhara T., Kise D., Yoshida H., Horita T., Murazaki Y., Nishimura A., Echigo N., Utsunomiya H., Tsuge H. Structural basis of the influenza A virus RNA polymerase PB2 RNA-binding domain containing the pathogenicity-determinant lysine 627 residue. J. Biol. Chem. 2009, 284(11):6855-6860.
99. Labadie K., Dos Santos Afonso E., Rameix-Welti M.A., van der Werf S., Naffakh N. Host-range determinants on the PB2 protein of influenza A viruses control the interaction between the viral polymerase and nucleoprotein in human cells. Virology 2007, 362(2):271-282.
100. Lam T.T., Wang J., Shen Y., Zhou B., Duan L., Cheung C.L., Ma C., Lycett S.J., Leung C.Y., Chen X., Li L., Hong W., Chai Y., Zhou L., Liang H., Ou Z., Liu Y., Farooqui A., Kelvin D.J., Poon L.L., Smith D.K., Pybus O.G., Leung G.M., Shu Y., Webster R.G., Webby R.J., Peiris J.S., Rambaut A., Zhu H., Guan Y. The genesis and source of the H7N9 influenza viruses causing human infections in China. Nature 2013, 502(7470):241-244.
101. Landeras-Bueno S., Jorba N., Perez-Cidoncha M., Ortin J. The splicing factor proline-glutamine rich (SFPQ/PSF) is involved in influenza virus transcription. PLoS Pathog. 2011, 7(11):e1002397.
102. Le Goffic R., Leymarie O., Chevalier C., Rebours E., Da Costa B., Vidic J., Descamps D., Sallenave J.M., Rauch M., Samson M., Delmas B. Transcriptomic analysis of host immune and cell death responses associated with the influenza A virus PB1-F2 protein. PLoS Pathog. 2011, 7(8):e1002202.
103. Le Q.M., Sakai-Tagawa Y., Ozawa M., Ito M., Kawaoka Y. Selection of H5N1 influenza virus PB2 during replication in humans. J. Virol. 2009, 83(10):5278-5281.
104. Lee T.G., Tomita J., Hovanessian A.G., Katze M.G. Characterization and regulation of the 58,00-dalton cellular inhibitor of the interferon-induced, dsRNA-activated protein kinase. J. Biol. Chem. 1992, 267:14238-14243.
105. Li G., Zhang J., Tong X., Liu W., Ye X. Heat shock protein 70 inhibits the activity of Influenza A virus ribonucleoprotein and blocks the replication of virus in vitro and in vivo. PloS One 2011, 6(2):e16546.
106. Li O.T., Chan M.C., Leung C.S., Chan R.W., Guan Y., Nicholls J.M., Poon L.L. Full factorial analysis of mammalian and avian influenza polymerase subunits suggests a role of an efficient polymerase for virus adaptation. PloS One 2009, 4(5):e5658.
107. Li X., Qi W., He J., Ning Z., Hu Y., Tian J., Jiao P., Xu C., Chen J., Richt J., Ma W., Liao M. Molecular basis of efficient replication and pathogenicity of H9N2 avian influenza viruses in mice. PloS One 2012, 7(6):e40118.
108. Li Z., Chen H., Jiao P., Deng G., Tian G., Li Y., Hoffmann E., Webster R.G., Matsuoka Y., Yu K. Molecular basis of replication of duck H5N1 influenza viruses in a mammalian mouse model. J. Virol. 2005, 79(18):12058-12064.
109. Lim K., Kim M., Lee M.K., Ko J., Hong S., Choi B.S. Biophysical characterization of sites of host adaptive mutation in the influenza A virus RNA polymerase PB2 RNA-binding domain. Int. J. Biochem. Cell Biol. 2014, 53:237-245.
110. Linster M., van Boheemen S., de Graaf M., Schrauwen E.J., Lexmond P., Manz B., Bestebroer T.M., Baumann J., van Riel D., Rimmelzwaan G.F., Osterhaus A.D., Matrosovich M., Fouchier R.A., Herfst S. Identification, characterization, and natural selection of mutations driving airborne transmission of A/H5N1 virus. Cell 2014, 157(2):329-339.
111. Liu Q., Qiao C., Marjuki H., Bawa B., Ma J., Guillossou S., Webby R.J., Richt J.A., Ma W. Combination of PB2 271A and SR polymorphism at positions 590/591 is critical for viral replication and virulence of swine influenza virus in cultured cells and in vivo. J. Virol. 2012, 86(2):1233-1237.
112. Lopez-Turiso J.A., Martinez C., Tanaka T., Ortin J. The synthesis of influenza virus negative-strand RNA takes place in insoluble complexes present in the nuclear matrix fraction. Virus Res. 1990, 16(3):325-337.
113. Lutz T., Stoger R., Nieto A. CHD6 is a DNA-dependent ATPase and localizes at nuclear sites of mRNA synthesis. FEBS Lett. 2006, 580(25):5851-5857.
114. Lu Y., Wambach M., Katze M.G., Krug R.M. Binding of the influenza virus NS1 protein to double-stranded RNA inhibits the activation of the protein kinase that phosphorylates the elF-2 translation initiation factor. Virology 1995, 214:222-228.
115. Llompart C.M., Nieto A., Rodriguez-Frandsen A. Specific residues of PB2 and PA influenza virus polymerase subunits confer the ability for RNA polymerase II degradation and virus pathogenicity in mice. J. Virol. 2014, 88(6):3455-3463.
116. Manzoor R., Sakoda Y., Nomura N., Tsuda Y., Ozaki H., Okamatsu M., Kida H. PB2 protein of a highly pathogenic avian influenza virus strain A/chicken/Yamaguchi/7/2004 (H5N1) determines its replication potential in pigs. J. Virol. 2009, 83(4):1572-1578.
117. Massin P., van der Werf S., Naffakh N. Residue 627 of PB2 is a determinant of cold sensitivity in RNA replication of avian influenza viruses. J. Virol. 2001, 75(11):5398-5404.
118. Mayer D., Molawi K., Martinez-Sobrido L., Ghanem A., Thomas S., Baginsky S., Grossmann J., Garcia-Sastre A., Schwemmle M. Identification of cellular interaction partners of the influenza virus ribonucleoprotein complex and polymerase complex using proteomic-based approaches. J. Proteome Res. 2007, 6(2):672-682.
119. Mazur I., Anhlan D., Mitzner D., Wixler L., Schubert U., Ludwig S. The proapoptotic influenza A virus protein PB1-F2 regulates viral polymerase activity by interaction with the PB1 protein. Cell. Microbiol. 2008, 10(5):1140-1152.
120. McAuley J.L., Chipuk J.E., Boyd K.L., Van De Velde N., Green D.R., McCullers J.A. PB1-F2 proteins from H5N1 and 20 century pandemic influenza viruses cause immunopathology. PLoS Pathog. 2010, 6(7):e1001014.
121. McAuley J.L., Hornung F., Boyd K.L., Smith A.M., McKeon R., Bennink J., Yewdell J.W., McCullers J.A. Expression of the 1918 influenza A virus PB1-F2 enhances the pathogenesis of viral and secondary bacterial pneumonia. Cell Host Microbe 2007, 2(4):240-249.
122. McAuley J.L., Tate M.D., MacKenzie-Kludas C.J., Pinar A., Zeng W., Stutz A., Latz E., Brown L.E., Mansell A. Activation of the NLRP3 inflammasome by IAV virulence protein PB1-F2 contributes to severe pathophysiology and disease. PLoS Pathog. 2013, 9(5):e1003392.
123. McAuley J.L., Zhang K., McCullers J.A. The effects of influenza A virus PB1-F2 protein on polymerase activity are strain specific and do not impact pathogenesis. J. Virol. 2010, 84(1):558-564.
124. Mehle A., Doudna J.A. An inhibitory activity in human cells restricts the function of an avian-like influenza virus polymerase. Cell Host Microbe 2008, 4(2):111-122.
125. Mehle A., Doudna J.A. Adaptive strategies of the influenza virus polymerase for replication in humans. Proc. Natl. Acad. Sci. U.S.A. 2009, 106(50):21312-21316.
126. Mehle A., Dugan V.G., Taubenberger J.K., Doudna J.A. Reassortment and mutation of the avian influenza virus polymerase PA subunit overcome species barriers. J. Virol. 2012, 86(3):1750-1757.
127. Menachery V.D., Eisfeld A.J., Schafer A., Josset L., Sims A.C., Proll S., Fan S., Li C., Neumann G., Tilton S.C., Chang J., Gralinski L.E., Long C., Green R., Williams C.M., Weiss J., Matzke M.M., Webb-Robertson B.J., Schepmoes A.A., Shukla A.K., Metz T.O., Smith R.D., Waters K.M., Katze M.G., Kawaoka Y., Baric R.S. Pathogenic influenza viruses and coronaviruses utilize similar and contrasting approaches to control interferon-stimulated gene responses. mBio 2014, 5(3). e01174-01114.
128. Mibayashi M., Martinez-Sobrido L., Loo Y.M., Cardenas W.B., Gale M., Garcia-Sastre A. Inhibition of retinoic acid-inducible gene I-mediated induction of beta interferon by the NS1 protein of influenza A virus. J. Virol. 2007, 81(2):514-524.
129. Min J.Y., Santos C., Fitch A., Twaddle A., Toyoda Y., DePasse J.V., Ghedin E., Subbarao K. Mammalian adaptation in the PB2 gene of avian H5N1 influenza virus. J. Virol. 2013, 87(19):10884-10888.
130. Mitzner D., Dudek S.E., Studtrucker N., Anhlan D., Mazur I., Wissing J., Jansch L., Wixler L., Bruns K., Sharma A., Wray V., Henklein P., Ludwig S., Schubert U. Phosphorylation of the influenza A virus protein PB1-F2 by PKC is crucial for apoptosis promoting functions in monocytes. Cell. Microbiol. 2009, 11(10):1502-1516.
131. Moeller A., Kirchdoerfer R.N., Potter C.S., Carragher B., Wilson I.A. Organization of the influenza virus replication machinery. Science 2012, 338(6114):1631-1634.
132. Mok C.K., Lee H.H., Lestra M., Nicholls J.M., Chan M.C., Sia S.F., Zhu H., Poon L.L., Guan Y., Peiris J.S. Amino acid substitutions in polymerase basic protein 2 gene contribute to the pathogenicity of the novel A/H7N9 influenza virus in mammalian hosts. J. Virol. 2014, 88(6):3568-3576.
133. Momose F., Naito T., Yano K., Sugimoto S., Morikawa Y., Nagata K. Identification of Hsp90 as a stimulatory host factor involved in influenza virus RNA synthesis. J. Biol. Chem. 2002, 277(47):45306-45314.
134. Moncorge O., Mura M., Barclay W.S. Evidence for avian and human host cell factors that affect the activity of influenza virus polymerase. J. Virol. 2010, 84(19):9978-9986.
135. Munier S., Rolland T., Diot C., Jacob Y., Naffakh N. Exploration of binary virus-host interactions using an infectious protein complementation assay. Mol. Cell. Proteom. MCP 2013, 12(10):2845-2855.
136. Munster V.J., de Wit E., van Riel D., Beyer W.E., Rimmelzwaan G.F., Osterhaus A.D., Kuiken T., Fouchier R.A. The molecular basis of the pathogenicity of the Dutch highly pathogenic human influenza A H7N7 viruses. J. Infect. Dis. 2007, 196(2):258-265.
137. Muramoto Y., Noda T., Kawakami E., Akkina R., Kawaoka Y. Identification of novel influenza A virus proteins translated from PA mRNA. J. Virol. 2013, 87(5):2455-2462.
138. Naffakh N., Massin P., Escriou N., Crescenzo-Chaigne B., van der Werf S. Genetic analysis of the compatibility between polymerase proteins from human and avian strains of influenza A viruses. J. Gen. Virol. 2000, 81(Pt 5):1283-1291.
139. Naffakh N., Tomoiu A., Rameix-Welti M.A., van der Werf S. Host restriction of avian influenza viruses at the level of the ribonucleoproteins. Ann. Rev. Microbiol. 2008, 62:403-424.
140. Nemeroff M.E., Barabino S.M., Li Y., Keller W., Krug R.M. Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3'end formation of cellular pre-mRNAs. Mol. Cell 1998, 1(7):991-1000.
141. Ozawa M., Basnet S., Burley L.M., Neumann G., Hatta M., Kawaoka Y. Impact of amino acid mutations in PB2, PB1-F2, and NS1 on the replication and pathogenicity of pandemic (H1N1) 2009 influenza viruses. J. Virol. 2011, 85(9):4596-4601.
142. Park Y.W., Katze M.G. Translational control by influenza virus. Identification of cis-acting sequences and trans-acting factors which may regulate selective viral mRNA translation. J. Biol. Chem. 1995, 270(47):28433-28439.
143. Pasricha G., Mishra A.C., Chakrabarti A.K. Comprehensive global amino acid sequence analysis of PB1F2 protein of influenza A H5N1 viruses and the influenza A virus subtypes responsible for the 20th-century pandemics. Influenza Respir. Viruses 2013, 7(4):497-505.
144. Perez-Gonzalez A., Rodriguez A., Huarte M., Salanueva I.J., Nieto A. hCLE/CGI-99, a human protein that interacts with the influenza virus polymerase, is a mRNA transcription modulator. J. Mol. Biol. 2006, 362(5):887-900.
145. Perez D.R., Donis R.O. Functional analysis of PA binding by influenza a virus PB1: effects on polymerase activity and viral infectivity. J. Virol. 2001, 75(17):8127-8136.
146. Perez J.T., Varble A., Sachidanandam R., Zlatev I., Manoharan M., Garcia-Sastre A., tenOever B.R. Influenza A virus-generated small RNAs regulate the switch from transcription to replication. Proc. Natl. Acad. Sci. U.S.A. 2010, 107(25):11525-11530.
147. Perez J.T., Zlatev I., Aggarwal S., Subramanian S., Sachidanandam R., Kim B., Manoharan M., tenOever B.R. A small-RNA enhancer of viral polymerase activity. J. Virol. 2012, 86(24):13475-13485.
148. Pflug A., Guilligay D., Reich S., Cusack S. Structure of influenza A polymerase bound to the viral RNA promoter. Nature 2014, 516(7531):355-360.
149. Ping J., Dankar S.K., Forbes N.E., Keleta L., Zhou Y., Tyler S., Brown E.G. PB2 and hemagglutinin mutations are major determinants of host range and virulence in mouse-adapted influenza A virus. J. Virol. 2010, 84(20):10606-10618.
150. Qi L., Carbone K.M., Ye Z., Liu T., Ovanesov M., Pletnikov M., Sauder C., Rubin S.A. Genetic contributions to influenza virus attenuation in the rat brain. J. Neurovirol. 2008, 14(2):136-142.
151. Reich S., Guilligay D., Pflug A., Malet H., Berger I., Crepin T., Hart D., Lunardi T., Nanao M., Ruigrok R.W., Cusack S. Structural insight into cap-snatching and RNA synthesis by influenza polymerase. Nature 2014, 516(7531):361-366.
152. Resa-Infante P., Gabriel G. The nuclear import machinery is a determinant of influenza virus host adaptation. BioEssays: News Rev. Mol. Cell. Dev. Biol. 2013, 35(1):23-27.
153. Resa-Infante P., Jorba N., Coloma R., Ortin J. The influenza virus RNA synthesis machine: advances in its structure and function. RNA Biol. 2011, 8(2):207-215.
154. Resa-Infante P., Jorba N., Zamarreno N., Fernandez Y., Juarez S., Ortin J. The host-dependent interaction of alpha-importins with influenza PB2 polymerase subunit is required for virus RNA replication. PloS One 2008, 3(12):e3904.
155. Resa-Infante P., Recuero-Checa M.A., Zamarreno N., Llorca O., Ortin J. Structural and functional characterization of an influenza virus RNA polymerase-genomic RNA complex. J. Virol. 2010, 84(20):10477-10487.
156. Rodriguez A., Falcon A., Cuevas M.T., Pozo F., Guerra S., Garcia-Barreno B., Martinez-Orellana P., Perez-Brena P., Montoya M., Melero J.A., Pizarro M., Ortin J., Casas I., Nieto A. Characterization in vitro and in vivo of a pandemic H1N1 influenza virus from a fatal case. PloS One 2013, 8(1):e53515.
157. Rodriguez A., Perez-Gonzalez A., Hossain M.J., Chen L.M., Rolling T., Perez-Brena P., Donis R., Kochs G., Nieto A. Attenuated strains of influenza A viruses do not induce degradation of RNA polymerase II. J. Virol. 2009, 83(21):11166-11174.
158. Rodriguez A., Perez-Gonzalez A., Nieto A. Influenza virus infection causes specific degradation of the largest subunit of cellular RNA polymerase II. J. Virol. 2007, 81(10):5315-5324.
159. Rodriguez A., Perez-Gonzalez A., Nieto A. Cellular human CLE/C14orf166 protein interacts with influenza virus polymerase and is required for viral replication. J. Virol. 2011, 85(22):12062-12066.
160. Rolling T., Koerner I., Zimmermann P., Holz K., Haller O., Staeheli P., Kochs G. Adaptive mutations resulting in enhanced polymerase activity contribute to high virulence of influenza A virus in mice. J. Virol. 2009, 83(13):6673-6680.
161. Russell C.A., Fonville J.M., Brown A.E., Burke D.F., Smith D.L., James S.L., Herfst S., van Boheemen S., Linster M., Schrauwen E.J., Katzelnick L., Mosterin A., Kuiken T., Maher E., Neumann G., Osterhaus A.D., Kawaoka Y., Fouchier R.A., Smith D.J. The potential for respiratory droplet-transmissible A/H5N1 influenza virus to evolve in a mammalian host. Science 2012, 336(6088):1541-1547.
162. Schmolke M., Manicassamy B., Pena L., Sutton T., Hai R., Varga Z.T., Hale B.G., Steel J., Perez D.R., Garcia-Sastre A. Differential contribution of PB1-F2 to the virulence of highly pathogenic H5N1 influenza A virus in mammalian and avian species. PLoS Pathog. 2011, 7(8):e1002186.
163. Schnitzler S.U., Schnitzler P. An update on swine-origin influenza virus A/H1N1: a review. Virus Genes 2009, 39(3):279-292.
164. Seyer R., Hrincius E.R., Ritzel D., Abt M., Mellmann A., Marjuki H., Kuhn J., Wolff T., Ludwig S., Ehrhardt C. Synergistic adaptive mutations in the hemagglutinin and polymerase acidic protein lead to increased virulence of pandemic 2009 H1N1 influenza A virus in mice. J. Infect. Dis. 2012, 205(2):262-271.
165. Shapira S.D., Gat-Viks I., Shum B.O., Dricot A., de Grace M.M., Wu L., Gupta P.B., Hao T., Silver S.J., Root D.E., Hill D.E., Regev A., Hacohen N. A physical and regulatory map of host-influenza interactions reveals pathways in H1N1 infection. Cell 2009, 139(7):1255-1267.
166. Shi M., Jagger B.W., Wise H.M., Digard P., Holmes E.C., Taubenberger J.K. Evolutionary conservation of the PA-X open reading frame in segment 3 of influenza A virus. J. Virol. 2012, 86(22):12411-12413.
167. Shinya K., Hamm S., Hatta M., Ito H., Ito T., Kawaoka Y. PB2 amino acid at position 627 affects replicative efficiency, but not cell tropism, of Hong Kong H5N1 influenza A viruses in mice. Virology 2004, 320(2):258-266.
168. Shinya K., Makino A., Ozawa M., Kim J.H., Sakai-Tagawa Y., Ito M., Le Q.M., Kawaoka Y. Ostrich involvement in the selection of H5N1 influenza virus possessing mammalian-type amino acids in the PB2 protein. J. Virol. 2009, 83(24):13015-13018.
169. Shinya K., Watanabe S., Ito T., Kasai N., Kawaoka Y. Adaptation of an H7N7 equine influenza A virus in mice. J. Gen. Virol. 2007, 88(Pt 2):547-553.
170. Snyder M.H., Betts R.F., DeBorde D., Tierney E.L., Clements M.L., Herrington D., Sears S.D., Dolin R., Maassab H.F., Murphy B.R. Four viral genes independently contribute to attenuation of live influenza A/Ann Arbor/6/60 (H2N2) cold-adapted reassortant virus vaccines. J. Virol. 1988, 62(2):488-495.
171. Snyder M.H., Clements M.L., De Borde D., Maassab H.F., Murphy B.R. Attenuation of wild-type human influenza A virus by acquisition of the PA polymerase and matrix protein genes of influenza A/Ann Arbor/6/60 cold-adapted donor virus. J. Clin. Microbiol. 1985, 22(5):719-725.
172. Song M.S., Pascua P.N., Lee J.H., Baek Y.H., Lee O.J., Kim C.J., Kim H., Webby R.J., Webster R.G., Choi Y.K. The polymerase acidic protein gene of influenza a virus contributes to pathogenicity in a mouse model. J. Virol. 2009, 83(23):12325-12335.
173. Sorrell E.M., Schrauwen E.J., Linster M., De Graaf M., Herfst S., Fouchier R.A. Predicting 'airborne' influenza viruses: (trans-) mission impossible?. Curr. Opin. Virol. 2011, 1(6):635-642.
174. Steel J., Lowen A.C., Mubareka S., Palese P. Transmission of influenza virus in a mammalian host is increased by PB2 amino acids 627K or 627E/701N. PLoS Pathog. 2009, 5(1):e1000252.
175. Subbarao E.K., London W., Murphy B.R. A single amino acid in the PB2 gene of influenza A virus is a determinant of host range. J. Virol. 1993, 67(4):1761-1764.
176. Subbarao K., Klimov A., Katz J., Regnery H., Lim W., Hall H., Perdue M., Swayne D., Bender C., Huang J., Hemphill M., Rowe T., Shaw M., Xu X., Fukuda K., Cox N. Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness. Science 1998, 279(5349):393-396.
177. Sugiyama K., Obayashi E., Kawaguchi A., Suzuki Y., Tame J.R., Nagata K., Park S.Y. Structural insight into the essential PB1-PB2 subunit contact of the influenza virus RNA polymerase. EMBO J. 2009, 28(12):1803-1811.
178. Sun Y., Xu Q., Shen Y., Liu L., Wei K., Sun H., Pu J., Chang K.C., Liu J. Naturally occurring mutations in the PA gene are key contributors to increased virulence of pandemic H1N1/09 influenza virus in mice. J. Virol. 2014, 88(8):4600-4604.
179. Tafforeau L., Chantier T., Pradezynski F., Pellet J., Mangeot P.E., Vidalain P.O., Andre P., Rabourdin-Combe C., Lotteau V. Generation and comprehensive analysis of an influenza virus polymerase cellular interaction network. J. Virol. 2011, 85(24):13010-13018.
180. Takizawa N., Watanabe K., Nouno K., Kobayashi N., Nagata K. Association of functional influenza viral proteins and RNAs with nuclear chromatin and sub-chromatin structure. Microbes Infect. Inst. Pasteur 2006, 8(3):823-833.
181. Tarendeau F., Boudet J., Guilligay D., Mas P.J., Bougault C.M., Boulo S., Baudin F., Ruigrok R.W., Daigle N., Ellenberg J., Cusack S., Simorre J.P., Hart D.J. Structure and nuclear import function of the C-terminal domain of influenza virus polymerase PB2 subunit. Nature Struct. Mol. Biol. 2007, 14(3):229-233.
182. Tarendeau F., Crepin T., Guilligay D., Ruigrok R.W., Cusack S., Hart D.J. Host determinant residue lysine 627 lies on the surface of a discrete, folded domain of influenza virus polymerase PB2 subunit. PLoS Pathog. 2008, 4(8):e1000136.
183. Taubenberger J.K., Morens D.M. 1918 Influenza: the mother of all pandemics. Emerg. Infect. Dis. 2006, 12(1):15-22.
184. Taubenberger J.K., Reid A.H., Lourens R.M., Wang R., Jin G., Fanning T.G. Characterization of the 1918 influenza virus polymerase genes. Nature 2005, 437(7060):889-893.
185. Tauber S., Ligertwood Y., Quigg-Nicol M., Dutia B.M., Elliott R.M. Behaviour of influenza A viruses differentially expressing segment 2 gene products in vitro and in vivo. J. Gen. Virol. 2012, 93(Pt 4):840-849.
186. Thangavel R.R., Bouvier N.M. Animal models for influenza virus pathogenesis, transmission, and immunology. J. Immunol. Methods 2014.
187. Torreira E., Schoehn G., Fernandez Y., Jorba N., Ruigrok R.W., Cusack S., Ortin J., Llorca O. Three-dimensional model for the isolated recombinant influenza virus polymerase heterotrimer. Nucl. Acids Res. 2007, 35(11):3774-3783.
188. Varga Z.T., Grant A., Manicassamy B., Palese P. Influenza virus protein PB1-F2 inhibits the induction of type I interferon by binding to MAVS and decreasing mitochondrial membrane potential. J. Virol. 2012, 86(16):8359-8366.
189. Varga Z.T., Ramos I., Hai R., Schmolke M., Garcia-Sastre A., Fernandez-Sesma A., Palese P. 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.
190. Vasin A.V., Temkina O.A., Egorov V.V., Klotchenko S.A., Plotnikova M.A., Kiselev O.I. Molecular mechanisms enhancing the proteome of influenza A viruses: an overview of recently discovered proteins. Virus Res. 2014, 185:53-63.
191. Vreede F.T., Brownlee G.G. Influenza virion-derived viral ribonucleoproteins synthesize both mRNA and cRNA in vitro. J. Virol. 2007, 81(5):2196-2204.
192. Vreede F.T., Chan A.Y., Sharps J., Fodor E. Mechanisms and functional implications of the degradation of host RNA polymerase II in influenza virus infected cells. Virology 2010, 396(1):125-134.
193. Vreede F.T., Jung T.E., Brownlee G.G. Model suggesting that replication of influenza virus is regulated by stabilization of replicative intermediates. J. Virol. 2004, 78(17):9568-9572.
194. Wang J., Sun Y., Xu Q., Tan Y., Pu J., Yang H., Brown E.G., Liu J. Mouse-adapted H9N2 influenza A virus PB2 protein M147L and E627 K mutations are critical for high virulence. PloS One 2012, 7(7):e40752.
195. Wang P., Song W., Mok B.W., Zhao P., Qin K., Lai A., Smith G.J., Zhang J., Lin T., Guan Y., Chen H. Nuclear factor 90 negatively regulates influenza virus replication by interacting with viral nucleoprotein. J. Virol. 2009, 83(16):7850-7861.
196. Wise H.M., Foeglein A., Sun J., Dalton R.M., Patel S., Howard W., Anderson E.C., Barclay W.S., Digard P. A complicated message: Identification of a novel PB1-related protein translated from influenza A virus segment 2 mRNA. J. Virol. 2009, 83(16):8021-8031.
197. Xu C., Hu W.B., Xu K., He Y.X., Wang T.Y., Chen Z., Li T.X., Liu J.H., Buchy P., Sun B. Amino acids 473V and 598P of PB1 from an avian-origin influenza A virus contribute to polymerase activity, especially in mammalian cells. J. Gen. Virol. 2012, 93(Pt 3):531-540.
198. Yángüez E., Nieto A. So similar, yet so different: selective translation of capped and polyadenylated viral mRNAs in the influenza virus infected cell. Virus Res. 2011, 156(March (1-2)):1-12.
199. Yángüez E., Rodriguez P., Goodfellow I., Nieto A. Influenza virus polymerase confers independence of the cellular cap-binding factor eIF4E for viral mRNA translation. Virology 2012, 422(January (2)):297-307.
200. Yamada S., Hatta M., Staker B.L., Watanabe S., Imai M., Shinya K., Sakai-Tagawa Y., Ito M., Ozawa M., Watanabe T., Sakabe S., Li C., Kim J.H., Myler P.J., Phan I., Raymond A., Smith E., Stacy R., Nidom C.A., Lank S.M., Wiseman R.W., Bimber B.N., O'Connor D.H., Neumann G., Stewart L.J., Kawaoka Y. Biological and structural characterization of a host-adapting amino acid in influenza virus. PLoS Pathog. 2010, 6(8):e1001034.
201. Yamayoshi S., Yamada S., Fukuyama S., Murakami S., Zhao D., Uraki R., Watanabe T., Tomita Y., Macken C., Neumann G., Kawaoka Y. Virulence-affecting amino acid changes in the PA protein of H7N9 influenza A viruses. J. Virol. 2014, 88(6):3127-3134.
202. Yuan P., Bartlam M., Lou Z., Chen S., Zhou J., He X., Lv Z., Ge R., Li X., Deng T., Fodor E., Rao Z., Liu Y. Crystal structure of an avian influenza polymerase PA(N) reveals an endonuclease active site. Nature 2009, 458(7240):909-913.
203. Zamarin D., Garcia-Sastre A., Xiao X., Wang R., Palese P. Influenza virus PB1-F2 protein induces cell death through mitochondrial ANT3 and VDAC1. PLoS Pathog. 2005, 1(1):e4.
204. Zamarin D., Ortigoza M.B., Palese P. Influenza A virus PB1-F2 protein contributes to viral pathogenesis in mice. J. Virol. 2006, 80(16):7976-7983.
205. Zell R., Krumbholz A., Eitner A., Krieg R., Halbhuber K.J., Wutzler P. Prevalence of PB1-F2 of influenza A viruses. J. Gen. Virol. 2007, 88(Pt 2):536-546.
206. Zhang H., Li X., Guo J., Li L., Chang C., Li Y., Bian C., Xu K., Chen H., Sun B. The PB2 E627 K mutation contributes to the high polymerase activity and enhanced replication of H7N9 influenza virus. J. Gen. Virol. 2014, 95(Pt 4):779-786.
207. Zhang J., Li G., Ye X. Cyclin T1/CDK9 interacts with influenza A virus polymerase and facilitates its association with cellular RNA polymerase II. J. Virol. 2010, 84(24):12619-12627.
208. Zhang S., Wang Q., Wang J., Mizumoto K., Toyoda T. Two mutations in the C-terminal domain of influenza virus RNA polymerase PB2 enhance transcription by enhancing cap-1 RNA binding activity. Biochim. Biophys. Acta 2012, 1819(1):78-83.
209. Zhang Y., Zhang Q., Kong H., Jiang Y., Gao Y., Deng G., Shi J., Tian G., Liu L., Liu J., Guan Y., Bu Z., Chen H. H5N1 hybrid viruses bearing 2009/H1N1 virus genes transmit in guinea pigs by respiratory droplet. Science 2013, 340(6139):1459-1463.
210. Zhang Z., Kim T., Bao M., Facchinetti V., Jung S.Y., Ghaffari A.A., Qin J., Cheng G., Liu Y.J. DDX1, DDX21, and DHX36 helicases form a complex with the adaptor molecule TRIF to sense dsRNA in dendritic cells. Immunity 2011, 34(6):866-878.
211. Zhao Z., Yi C., Zhao L., Wang S., Zhou L., Hu Y., Zou W., Chen H., Jin M. PB2-588I enhances 2009 H1N1 pandemic influenza virus virulence by increasing viral replication and exacerbating PB2 inhibition of beta interferon expression. J. Virol. 2014, 88(4):2260-2267.
212. Zhou B., Li Y., Halpin R., Hine E., Spiro D.J., Wentworth D.E. PB2 residue 158 is a pathogenic determinant of pandemic H1N1 and H5 influenza a viruses in mice. J. Virol. 2011, 85(1):357-365.
213. Zhou J., To K.K., Dong H., Cheng Z.S., Lau C.C., Poon V.K., Fan Y.H., Song Y.Q., Tse H., Chan K.H., Zheng B.J., Zhao G.P., Yuen K.Y. A functional variation in CD55 increases the severity of 2009 pandemic H1N1 influenza A virus infection. J. Infect. Dis. 2012, 206(4):495-503.
214. Zhu H., Wang J., Wang P., Song W., Zheng Z., Chen R., Guo K., Zhang T., Peiris J.S., Chen H., Guan Y. Substitution of lysine at 627 position in PB2 protein does not change virulence of the 2009 pandemic H1N1 virus in mice. Virology 2010, 401(1):1-5.
215. Zhu W., Zhu Y., Qin K., Yu Z., Gao R., Yu H., Zhou J., Shu Y. Mutations in polymerase genes enhanced the virulence of 2009 pandemic H1N1 influenza virus in mice. PloS One 2012, 7(3):e33383.