Apoptosis, cytokine and chemokine induction by non-structural 1 (NS1) proteins encoded by different influenza subtypes

Virology Journal

Volumn 8, Issue , 2011, Pages

  Lam, W Y ^a   Yeung, Apple C M ^a   Chan, Paul K S ^a,b  

^a CHINESE UNIVERSITY OF HONG KONG   (Hong Kong)

^b and Hong Kong Branch of CAS Center for Excellence in Animal Evolution and Genetics   (Hong Kong)

Author keywords

Apoptosis; Avian influenza; Hypercytokinemia; Inflammation; NS1; Pandemic influenza; Pathogenesis

Indexed keywords

CHEMOKINE; CXCL9 CHEMOKINE; CYTOKINE; GAMMA INTERFERON INDUCIBLE PROTEIN 10; INTERLEUKIN 6; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; MESSENGER RNA; MONOCYTE CHEMOTACTIC PROTEIN 1; NONSTRUCTURAL PROTEIN 1; RANTES;

2009 H1N1 INFLUENZA; APOPTOSIS; ARTICLE; CONTROLLED STUDY; CYTOKINE PRODUCTION; GENE EXPRESSION PROFILING; HUMAN; HUMAN CELL; IN VITRO STUDY; INFLAMMATION; INFLUENZA; INFLUENZA VIRUS; INFLUENZA VIRUS A H2N2; INFLUENZA VIRUS A H3N2; INFLUENZA VIRUS A H5N1; INFLUENZA VIRUS A H7N3; INFLUENZA VIRUS A H9N2; LUNG ALVEOLUS EPITHELIUM; NONHUMAN; PANDEMIC INFLUENZA; PATHOGENESIS; PATHOGENICITY; SEASONAL INFLUENZA; TRANSIENT TRANSFECTION;

ANIMALS; APOPTOSIS; BIRDS; CELLS, CULTURED; CHEMOKINES, CC; CHEMOKINES, CXC; CYTOKINES; EPITHELIAL CELLS; HUMANS; INFLUENZA A VIRUS; INFLUENZA IN BIRDS; INFLUENZA, HUMAN; INTERLEUKIN-6; LUNG; RNA, MESSENGER; RNA, VIRAL; SPECIES SPECIFICITY; TRANSFECTION; VIRAL NONSTRUCTURAL PROTEINS;

AVES; ORTHOMYXOVIRIDAE; SUIDAE;

EID: 83755228813     PISSN: None     EISSN: 1743422X     Source Type: Journal    
DOI: 10.1186/1743-422X-8-554     Document Type: Article

References (73)

1. Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus. Claas EC, Osterhaus AD, van Beek R, De Jong JC, Rimmelzwaan GF, Senne DA, Krauss S, Shortridge KF, Webster RG, Lancet 1998 351 472 477 10.1016/S0140-6736(97)11212-0 9482438 (Pubitemid 28070093)
2. Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus. Yuen KY, Chan PK, Peiris M, Tsang DN, Que TL, Shortridge KF, Cheung PT, To WK, Ho ET, Sung R, et al. Lancet 1998 351 467 471 10.1016/S0140-6736(98)01182-9 9482437 (Pubitemid 28070092)
3. Human infection with influenza H9N2. Peiris M, Yuen KY, Leung CW, Chan KH, Ip PL, Lai RW, Orr WK, Shortridge KF, Lancet 1999 354 916 917 10.1016/S0140-6736(99)03311-5 10489954 (Pubitemid 29424025)
4. Pathology of fatal human infection associated with avian influenza A H5N1 virus. To KF, Chan PK, Chan KF, Lee WK, Lam WY, Wong KF, Tang NL, Tsang DN, Sung RY, Buckley TA, et al. J Med Virol 2001 63 242 246 10.1002/1096- 9071(200103)63:3<242::AID-JMV1007>3.0.CO;2-N 11170064 (Pubitemid 32116480)
5. Outbreak of avian influenza A(H5N1) virus infection in Hong Kong in 1997. Chan PK, Clin Infect Dis 2002 34 Suppl 2 58 S64 11938498
6. Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome. Fouchier RA, Schneeberger PM, Rozendaal FW, Broekman JM, Kemink SA, Munster V, Kuiken T, Rimmelzwaan GF, Schutten M, Van Doornum GJ, et al. Proc Natl Acad Sci USA 2004 101 1356 1361 10.1073/pnas.0308352100 14745020 (Pubitemid 38182693)
7. Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors. Yamada S, Suzuki Y, Suzuki T, Le MQ, Nidom CA, Sakai-Tagawa Y, Muramoto Y, Ito M, Kiso M, Horimoto T, et al. Nature 2006 444 378 382 10.1038/nature05264 17108965 (Pubitemid 44764114)
8. Update on avian influenza A (H5N1) virus infection in humans. Abdel-Ghafar AN, Chotpitayasunondh T, Gao Z, Hayden FG, Nguyen DH, de Jong MD, Naghdaliyev A, Peiris JS, Shindo N, Soeroso S, et al. N Engl J Med 2008 358 261 273 18199865
9. Cumulative number of confirmed human cases of avian influenza A/(H5N1) reported to WHO. World Health Organization, World Health Organization, Geneva, Switzerland 2011 http://www.who.int/influenza/human-animal-interface/EN-GIP- 20111215CumulativeNumberH5N1cases.pdf
10. Update: influenza activity-United States, August 30, 2009-March 27, 2010, and composition of the 2010-11 influenza vaccine. Centers for Disease Control and Prevention (CDC), Morb Mortal Wkly Rep 2010 59 423 430
11. Clinical aspects of pandemic 2009 influenza A (H1N1) virus infection. Bautista E, Chotpitayasunondh T, Gao Z, Harper SA, Shaw M, Uyeki TM, Zaki SR, Hayden FG, Hui DS, Kettner JD, et al. N Engl J Med 2010 362 1708 1719 20445182
12. Viral clearance and inflammatory response patterns in adults hospitalized for pandemic 2009 influenza A(H1N1) virus pneumonia. Lee N, Chan PK, Wong CK, Wong KT, Choi KW, Joynt GM, Lam P, Chan MC, Wong BC, Lui GC, Sin WW, Wong RY, Lam WY, Yeung AC, Leung TF, So HY, Yu AW, Sung JJ, Hui DS, Antivir Ther 2011 16:237 47 10.3851/IMP1722 21447873
13. Re-emergence of fatal human influenza A subtype H5N1 disease. Peiris JS, Yu WC, Leung CW, Cheung CY, Ng WF, Nicholls JM, Ng TK, Chan KH, Lai ST, Lim WL, et al. Lancet 2004 363 617 619 10.1016/S0140-6736(04)15595-5 14987888 (Pubitemid 38264181)
14. Avian influenza A (H5N1). de Jong MD, Hien TT, J Clin Virol 2006 35 2 13 10.1016/j.jcv.2005.09.002 16213784 (Pubitemid 43020946)
15. Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. de Jong MD, Simmons CP, Thanh TT, Hien VM, Smith GJ, Chau TN, Hoang DM, Chau NV, Khanh TH, Dong VC, et al. Nat Med 2006 12 1203 1207 10.1038/nm1477 16964257 (Pubitemid 44527358)
16. H5N1 transmission and disease: observations from the frontlines. de Jong MD, Pediatr Infect Dis J 2008 27 54 S56 10.1097/INF.0b013e3181684d2d 18820578
17. Role of apoptosis and cytokines in influenza virus morbidity. Brydon EW, Morris SJ, Sweet C, FEMS Microbiol Rev 2005 29 837 850 10.1016/j.femsre.2004.12. 003 16102605 (Pubitemid 41139183)
18. Pathology, molecular biology, and pathogenesis of avian influenza A (H5N1) infection in humans. Korteweg C, Gu J, Am J Pathol 2008 172 1155 1170 10.2353/ajpath.2008.070791 18403604 (Pubitemid 351671530)
19. Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Hatta M, Gao P, Halfmann P, Kawaoka Y, Science 2001 293 1840 1842 10.1126/science.1062882 11546875 (Pubitemid 32845783)
20. Cellular transcriptional profiling in influenza A virus-infected lung epithelial cells: the role of the nonstructural NS1 protein in the evasion of the host innate defense and its potential contribution to pandemic influenza. Geiss GK, Salvatore M, Tumpey TM, Carter VS, Wang X, Basler CF, Taubenberger JK, Bumgarner RE, Palese P, Katze MG, et al. Proc Natl Acad Sci USA 2002 99 10736 10741 10.1073/pnas.112338099 12149435
21. Pathogenicity and immunogenicity of influenza viruses with genes from the 1918 pandemic virus. Tumpey TM, Garcia-Sastre A, Taubenberger JK, Palese P, Swayne DE, Basler CF, Proc Natl Acad Sci USA 2004 101 3166 3171 10.1073/pnas.0308391100 14963236 (Pubitemid 38327752)
22. A single amino acid substitution in 1918 influenza virus hemagglutinin changes receptor binding specificity. Glaser L, Stevens J, Zamarin D, Wilson IA, Garcia-Sastre A, Tumpey TM, Basler CF, Taubenberger JK, Palese P, J Virol 2005 79 11533 11536 10.1128/JVI.79.17.11533-11536.2005 16103207 (Pubitemid 41170697)
23. Characterization of the reconstructed 1918 Spanish influenza pandemic virus. Tumpey TM, Basler CF, Aguilar PV, Zeng H, Solorzano A, Swayne DE, Cox NJ, Katz JM, Taubenberger JK, Palese P, et al. Science 2005 310 77 80 10.1126/science.1119392 16210530 (Pubitemid 41434537)
24. Genomic analysis of increased host immune and cell death responses induced by 1918 influenza virus. Kash JC, Tumpey TM, Proll SC, Carter V, Perwitasari O, Thomas MJ, Basler CF, Palese P, Taubenberger JK, Garcia-Sastre A, et al. Nature 2006 443 578 581 17006449 (Pubitemid 44527293)
25. The origin and virulence of the 1918 "Spanish" influenza virus. Taubenberger JK, Proc Am Philos Soc 2006 150 86 112 17526158
26. Influenza A virus PB1-F2 protein contributes to viral pathogenesis in mice. Zamarin D, Ortigoza MB, Palese P, J Virol 2006 80 7976 7983 10.1128/JVI.00415-06 16873254 (Pubitemid 44182298)
27. Polygenic virulence factors involved in pathogenesis of 1997 Hong Kong H5N1 influenza viruses in mice. Chen H, Bright RA, Subbarao K, Smith C, Cox NJ, Katz JM, Matsuoka Y, Virus Res 2007 128 159 163 10.1016/j.virusres.2007.04.017 17521765 (Pubitemid 47242890)
28. Growth of H5N1 influenza A viruses in the upper respiratory tracts of mice. Hatta M, Hatta Y, Kim JH, Watanabe S, Shinya K, Nguyen T, Lien PS, Le QM, Kawaoka Y, PLoS Pathog 2007 3 1374 1379 17922570 (Pubitemid 350085602)
29. Model suggesting that replication of influenza virus is regulated by stabilization of replicative intermediates. Vreede FT, Jung TE, Brownlee GG, J Virol 2004 78 9568 9572 10.1128/JVI.78.17.9568-9572.2004 15308750 (Pubitemid 39096565)
30. Defective RNA replication and late gene expression in temperature-sensitive influenza viruses expressing deleted forms of the NS1 protein. Falcon AM, Marion RM, Zurcher T, Gomez P, Portela A, Nieto A, Ortin J, J Virol 2004 78 3880 3888 10.1128/JVI.78.8.3880-3888.2004 15047804 (Pubitemid 38437194)
31. A site on the influenza A virus NS1 protein mediates both inhibition of PKR activation and temporal regulation of viral RNA synthesis. Min JY, Li S, Sen GC, Krug RM, Virology 2007 363 236 243 10.1016/j.virol.2007.01.038 17320139 (Pubitemid 46678175)
32. Influenza A virus NS1 protein binds p85beta and activates phosphatidylinositol-3-kinase signaling. Hale BG, Jackson D, Chen YH, Lamb RA, Randall RE, Proc Natl Acad Sci USA 2006 103 14194 14199 10.1073/pnas.0606109103 16963558 (Pubitemid 44453002)
33. Influenza A virus NS1 protein activates the PI3K/Akt pathway to mediate antiapoptotic signaling responses. Ehrhardt C, Wolff T, Pleschka S, Planz O, Beermann W, Bode JG, Schmolke M, Ludwig S, J Virol 2007 81 3058 3067 10.1128/JVI.02082-06 17229704 (Pubitemid 46456615)
34. Influenza A virus NS1 protein activates the phosphatidylinositol 3-kinase (PI3K)/Akt pathway by direct interaction with the p85 subunit of PI3K. Shin YK, Liu Q, Tikoo SK, Babiuk LA, Zhou Y, J Gen Virol 2007 88 13 18 10.1099/vir.0.82419-0 17170431 (Pubitemid 46085109)
35. Control of apoptosis in influenza virus-infected cells by up-regulation of Akt and p53 signaling. Zhirnov OP, Klenk HD, Apoptosis 2007 12 1419 1432 10.1007/s10495-007-0071-y 17468837 (Pubitemid 46988278)
36. 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. Min JY, Krug RM, Proc Natl Acad Sci USA 2006 103 7100 7105 10.1073/pnas. 0602184103 16627618
37. Activation of interferon regulatory factor 3 is inhibited by the influenza A virus NS1 protein. Talon J, Horvath CM, Polley R, Basler CF, Muster T, Palese P, Garcia-Sastre A, J Virol 2000 74 7989 7996 10.1128/JVI.74.17.7989- 7996.2000 10933707 (Pubitemid 30641643)
38. Influenza A virus NS1 protein prevents activation of NF-kappaB and induction of alpha/beta interferon. Wang X, Li M, Zheng H, Muster T, Palese P, Beg AA, Garcia-Sastre A, J Virol 2000 74 11566 11573 10.1128/JVI.74.24.11566- 11573.2000 11090154 (Pubitemid 32222305)
39. The influenza A virus NS1 protein inhibits activation of Jun N-terminal kinase and AP-1 transcription factors. Ludwig S, Wang X, Ehrhardt C, Zheng H, Donelan N, Planz O, Pleschka S, Garcia-Sastre A, Heins G, Wolff T, J Virol 2002 76 11166 11171 10.1128/JVI.76.21.11166-11171.2002 12368362 (Pubitemid 35176236)
40. NS1 protein of influenza A virus inhibits the function of intracytoplasmic pathogen sensor, RIG-I. Guo Z, Chen LM, Zeng H, Gomez JA, Plowden J, Fujita T, Katz JM, Donis RO, Sambhara S, Am J Respir Cell Mol Biol 2007 36 263 269 17053203 (Pubitemid 46365276)
41. Inhibition of retinoic acid-inducible gene I-mediated induction of beta interferon by the NS1 protein of influenza A virus. Mibayashi M, Martinez-Sobrido L, Loo YM, Cardenas WB, Gale M, Garcia-Sastre A, J Virol 2007 81 514 524 10.1128/JVI.01265-06 17079289 (Pubitemid 46067878)
42. IFNbeta induction by influenza A virus is mediated by RIG-I which is regulated by the viral NS1 protein. Opitz B, Rejaibi A, Dauber B, Eckhard J, Vinzing M, Schmeck B, Hippenstiel S, Suttorp N, Wolff T, Cell Microbiol 2007 9 930 938 10.1111/j.1462-5822.2006.00841.x 17140406 (Pubitemid 46394904)
43. Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3'end formation of cellular pre-mRNAs. Nemeroff ME, Barabino SM, Li Y, Keller W, Krug RM, Mol Cell 1998 1 991 1000 10.1016/S1097-2765(00) 80099-4 9651582 (Pubitemid 128379260)
44. 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. Noah DL, Twu KY, Krug RM, Virology 2003 307 386 395 10.1016/S0042-6822(02)00127-7 12667806 (Pubitemid 36344169)
45. Influenza virus NS1 protein counteracts PKR-mediated inhibition of replication. Bergmann M, Garcia-Sastre A, Carnero E, Pehamberger H, Wolff K, Palese P, Muster T, J Virol 2000 74 6203 6206 10.1128/JVI.74.13.6203-6206.2000 10846107 (Pubitemid 30412995)
46. A new influenza virus virulence determinant: the NS1 protein four C-terminal residues modulate pathogenicity. Jackson D, Hossain MJ, Hickman D, Perez DR, Lamb RA, Proc Natl Acad Sci USA 2008 105 4381 4386 10.1073/pnas.0800482105 18334632 (Pubitemid 351754389)
47. Influenza virus evades innate and adaptive immunity via the NS1 protein. Fernandez-Sesma A, Marukian S, Ebersole BJ, Kaminski D, Park MS, Yuen T, Sealfon SC, Garcia-Sastre A, Moran TM, J Virol 2006 80 6295 6304 10.1128/JVI.02381-05 16775317 (Pubitemid 43927432)
48. Expression of IL-6, IL-8, and RANTES on human bronchial epithelial cells, NCI-H292, induced by influenza virus A. Matsukura S, Kokubu F, Noda H, Tokunaga H, Adachi M, J Allergy Clin Immunol 1996 98 1080 1087 10.1016/S0091-6749(96) 80195-3 8977509 (Pubitemid 27014801)
49. Tumor necrosis factor alpha exerts powerful anti-influenza virus effects in lung epithelial cells. Seo SH, Webster RG, J Virol 2002 76 1071 1076 10.1128/JVI.76.3.1071-1076.2002 11773383 (Pubitemid 34066411)
50. Susceptibility of mononuclear phagocytes to influenza A virus infection and possible role in the antiviral response. Hofmann P, Sprenger H, Kaufmann A, Bender A, Hasse C, Nain M, Gemsa D, J Leukoc Biol 1997 61 408 414 9103226 (Pubitemid 27219833)
51. Induction of proinflammatory cytokines in human macrophages by influenza A (H5N1) viruses: a mechanism for the unusual severity of human disease? Cheung CY, Poon LL, Lau AS, Luk W, Lau YL, Shortridge KF, Gordon S, Guan Y, Peiris JS, Lancet 2002 360 1831 1837 10.1016/S0140-6736(02)11772-7 12480361 (Pubitemid 35449422)
52. Induction of proinflammatory cytokines in primary human macrophages by influenza A virus (H5N1) is selectively regulated by IFN regulatory factor 3 and p38 MAPK. Hui KP, Lee SM, Cheung CY, Ng IH, Poon LL, Guan Y, Ip NY, Lau AS, Peiris JS, J Immunol 2009 182 1088 1098 19124752
53. Expression of cytokines on human bronchial epithelial cells induced by influenza virus A. Adachi M, Matsukura S, Tokunaga H, Kokubu F, Int Arch Allergy Immunol 1997 113 307 311 10.1159/000237584 9130560 (Pubitemid 27160796)
54. Tumor necrosis factor-alpha production of influenza A virus-infected macrophages and potentiating effect of lipopolysaccharides. Nain M, Hinder F, Gong JH, Schmidt A, Bender A, Sprenger H, Gemsa D, J Immunol 1990 145 1921 1928 2391423 (Pubitemid 20336764)
55. Influenza virus A infection induces interleukin-8 gene expression in human airway epithelial cells. Choi AM, Jacoby DB, FEBS Lett 1992 309 327 329 10.1016/0014-5793(92)80799-M 1516705
56. Differential mononuclear leukocyte attracting chemokine production after stimulation with active and inactivated influenza A virus. Bussfeld D, Kaufmann A, Meyer RG, Gemsa D, Sprenger H, Cell Immunol 1998 186 1 7 10.1006/cimm.1998. 1295 9637759 (Pubitemid 28285342)
57. Expression of RANTES by normal airway epithelial cells after influenza virus A infection. Matsukura S, Kokubu F, Kubo H, Tomita T, Tokunaga H, Kadokura M, Yamamoto T, Kuroiwa Y, Ohno T, Suzaki H, et al. Am J Respir Cell Mol Biol 1998 18 255 264 9476913 (Pubitemid 128355199)
58. Inflammatory responses in influenza A virus infection. Julkunen I, Melen K, Nyqvist M, Pirhonen J, Sareneva T, Matikainen S, Vaccine 2000 19 Suppl 1 32 S37 11163460
59. Influenza A and sendai viruses induce differential chemokine gene expression and transcription factor activation in human macrophages. Matikainen S, Pirhonen J, Miettinen M, Lehtonen A, Govenius-Vintola C, Sareneva T, Julkunen I, Virology 2000 276 138 147 10.1006/viro.2000.0542 11022002
60. Molecular pathogenesis of influenza A virus infection and virus-induced regulation of cytokine gene expression. Julkunen I, Sareneva T, Pirhonen J, Ronni T, Melen K, Matikainen S, Cytokine Growth Factor Rev 2001 12 171 180 10.1016/S1359-6101(00)00026-5 11325600 (Pubitemid 32588143)
61. Influenza A virus-induced apoptosis in bronchiolar epithelial (NCI-H292) cells limits pro-inflammatory cytokine release. Brydon EW, Smith H, Sweet C, J Gen Virol 2003 84 2389 2400 10.1099/vir.0.18913-0 12917460 (Pubitemid 37063128)
62. Profiles of cytokine and chemokine gene expression in human pulmonary epithelial cells induced by human and avian influenza viruses. Lam WY, Yeung AC, Chu IM, Chan PK, Virol J 2010 7 344 10.1186/1743-422X-7-344 21108843
63. The stability of mRNA influences the temporal order of the induction of genes encoding inflammatory molecules. Hao S, Baltimore D, Nat Immunol 2009 10 281 288 19198593
64. Influenza H5N1 and H1N1 virus replication and innate immune responses in bronchial epithelial cells are influenced by the state of differentiation. Chan RW, Yuen KM, Yu WC, Ho CC, Nicholls JM, Peiris JS, Chan MC, PLoS One 2010 5 8713 10.1371/journal.pone.0008713 20090947
65. Pandemic H1N1 2009 influenza A virus induces weak cytokine responses in human macrophages and dendritic cells and is highly sensitive to the antiviral actions of interferons. Osterlund P, Pirhonen J, Ikonen N, Ronkko E, Strengell M, Makela SM, Broman M, Hamming OJ, Hartmann R, Ziegler T, et al. J Virol 2010 84 1414 1422 10.1128/JVI.01619-09 19939920
66. Cytokine profiles induced by the novel swine-origin influenza A/H1N1 virus: implications for treatment strategies. Woo PC, Tung ET, Chan KH, Lau CC, Lau SK, Yuen KY, J Infect Dis 2010 201 346 353 10.1086/649785 20030555
67. Comparison of pro-inflammatory cytokine expression and cellular signal transduction in human macrophages infected with different influenza A viruses. Geiler J, Michaelis M, Sithisarn P, Cinatl J Jr, Med Microbiol Immunol 2011 200 53 60 10.1007/s00430-010-0173-y 20865277
68. Differential onset of apoptosis in influenza A virus. Mok CK, Lee DC, Cheung CY, Peiris M, Lau AS, J Gen Virol 2007 88 1275 1280 10.1099/vir.0.82423-0 17374772 (Pubitemid 46523517)
69. Influenza virus ns1 protein induces apoptosis in cultured cells. Schultz-Cherry S, Dybdahl-Sissoko N, Neumann G, Kawaoka Y, Hinshaw VS, J Virol 2001 75 7875 7881 10.1128/JVI.75.17.7875-7881.2001 11483732 (Pubitemid 32743659)
70. NS1 protein of influenza A virus down-regulates apoptosis. Zhirnov OP, Konakova TE, Wolff T, Klenk HD, J Virol 2002 76 1617 1625 10.1128/JVI.76.4.1617- 1625.2002 11799156 (Pubitemid 34094608)
71. Influenza A mutant viruses with altered NS1 protein function provoke caspase-1 activation in primary human macrophages, resulting in fast apoptosis and release of high levels of interleukins 1beta and 18. Stasakova J, Ferko B, Kittel C, Sereinig S, Romanova J, Katinger H, Egorov A, J Gen Virol 2005 86 185 195 10.1099/vir.0.80422-0 15604446 (Pubitemid 40081165)
72. The multifunctional NS1 protein of influenza A viruses. Hale BG, Randall RE, Ortin J, Jackson D, J Gen Virol 2008 89 2359 2376 10.1099/vir.0.2008/004606- 0 18796704
73. Avian influenza virus A/HK/483/97(H5N1) NS1 protein induces apoptosis in human airway epithelial cells. Lam WY, Tang JW, Yeung AC, Chiu LC, Sung JJ, Chan PK, J Virol 2008 82 2741 2751 10.1128/JVI.01712-07 18199656 (Pubitemid 351329165)