Pathogenesis of influenza virus infections: The good, the bad and the ugly

Current Opinion in Virology

Volumn 2, Issue 3, 2012, Pages 276-286

  Kuiken, T ^a   Riteau, B ^b,c   Fouchier, R A M ^a   Rimmelzwaan, G F ^a  

^a ERASMUS MEDICAL CENTER   (Netherlands)

^b UNIVERSITÉ DE LYON   (France)

^c UMR ASTRE   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ADAPTIVE IMMUNITY; HOST RESISTANCE; HUMAN; IMMUNE DYSREGULATION; IMMUNITY; INFLUENZA; INFLUENZA VIRUS; INNATE IMMUNITY; LUNG INJURY; NONHUMAN; PNEUMONIA; PRIORITY JOURNAL; REVIEW; UPPER RESPIRATORY TRACT INFECTION; VIRAL TROPISM; VIRUS GENE; VIRUS PATHOGENESIS; VIRUS REPLICATION;

ANIMALS; HUMANS; INFLUENZA, HUMAN; LUNG; ORTHOMYXOVIRIDAE; ORTHOMYXOVIRIDAE INFECTIONS; VIRAL TROPISM; VIRULENCE; VIRULENCE FACTORS;

EID: 84862840222     PISSN: 18796257     EISSN: 18796265     Source Type: Journal    
DOI: 10.1016/j.coviro.2012.02.013     Document Type: Review

References (117)

1. Kumar V, Abbas AK, Fausto N: Cellular adaptations, cell injury, and cell death. In Pathologic Basis of Disease, edn 7. Edited by Robbins, Cotran.Elsevier Saunders; 1999:3-46.
2. van Riel D, den Bakker MA, Leijten LM, Chutinimitkul S, Munster VJ, de Wit E, Rimmelzwaan GF, Fouchier RA, Osterhaus AD, Kuiken T: Seasonal and pandemic human influenza viruses attach better to human upper respiratory tract epithelium than avian influenza viruses. Am J Pathol 2010, 176:1614-1618. This article shows that efficient transmissibility of influenza viruses among humans is linked to abundant virus attachment to the human upper respiratory tract.
3. van Riel D, Munster VJ, de Wit E, Rimmelzwaan GF, Fouchier RA, Osterhaus AD, Kuiken T: Human and avian influenza viruses target different cells in the lower respiratory tract of humans and other mammals. Am J Pathol 2007, 171:1215-1223. (Pubitemid 47582895)
4. Thompson CI, Barclay WS, Zambon MC, Pickles RJ: Infection of human airway epithelium by human and avian strains of influenza A virus. J Virol 2006, 80:8060-8068. (Pubitemid 44182306)
5. Zambon MC: Epidemiology and pathogenesis of influenza. J Antimicrob Chemother 1999, 44(Suppl. B):3-9.
6. Walsh JJ, Dietlein LF, Low FN, Burch GE, Mogabgab WJ: Bronchotracheal response in human influenza. Type A, Asian strain, as studied by light and electron microscopic examination of bronchoscopic biopsies. Arch Intern Med 1961, 108:376-388.
7. van Riel D, Munster VJ, de Wit E, Rimmelzwaan GF, Fouchier RA, Osterhaus AD, Kuiken T: H5N1 virus attachment to lower respiratory tract. Science 2006, 312:399.
8. Shinya K, Ebina M, Yamada S, Ono M, Kasai N, Kawaoka Y: Avian flu: influenza virus receptors in the human airway. Nature 2006, 440:435-436.
9. Sorrell EM, Schrauwen EJA, Linster M, De Graaf M, Herfst S, Fouchier RAM: Predicting 'airborne' influenza viruses: (trans-) mission impossible? Curr Opin Virol 2011, 1:635-642.
10. Nicholls JM, Chan MC, Chan WY, Wong HK, Cheung CY, Kwong DL, Wong MP, Chui WH, Poon LL, Tsao SW et al.: Tropism of avian influenza A (H5N1) in the upper and lower respiratory tract. Nat Med 2007, 13:147-149.
11. Balogh K: Mouth, nose and paranasal sinuses. In Histology for Pathologists, edn 2. Edited by Sternberg SS. Lippincott-Raven Publishers; 1997:367-389.
12. Schrauwen EJA, Herfst S, Leijten LM, van Run P, Bestebroer TM, Linster M, Bodewes R, Kreijtz JHCM, Rimmelzwaan GF, Osterhaus ADME, et al.: The multi basic cleavage site in H5N1 virus is critical for systemic spread along the olfactory and hematogenous routes in ferrets. J Virol, doi:10.1128/JVI.06828- 11, in press This article shows that intranasally inoculated HPAI H5N1 virus in ferrets reaches the brain from the olfactory mucosa via the olfactory bulb, and that the multibasic cleavage site in the hemagglutinin is required for this route of entry.
13. Bodewes R, Kreijtz JH, van Amerongen G, Fouchier RA, Osterhaus AD, Rimmelzwaan GF, Kuiken T: Pathogenesis of Influenza A/H5N1 virus infection in ferrets differs between intranasal and intratracheal routes of inoculation. Am J Pathol 2011, 179:30-36. This article shows that intranasal inoculation of HPAI H5N1 virus in ferrets causes severe encephalomyelitis, while intratracheal inoculation of the same virus causes severe pneumonia. This emphasizes the importance of route of inoculation for animal models of HPAI H5N1.
14. de Jong MD, Bach VC, Phan TQ, Vo MH, Tran TT, Nguyen BH, Beld M, Le TP, Truong HK, Nguyen VV et al.: Fatal avian influenza A (H5N1) in a child presenting with diarrhea followed by coma. N Engl J Med 2005, 352:686-691. (Pubitemid 40239216)
15. Kuiken T, Taubenberger JK: Pathology of human influenza revisited. Vaccine 2008, 26(Suppl. 4):D59-D66.
16. Belser JA, Zeng H, Katz JM, Tumpey TM: Ocular tropism of influenza A viruses: identification of H7 subtype-specific host responses in human respiratory and ocular cells. J Virol 2011, 85:10117-10125.
17. Yu WC, Chan RW, Wang J, Travanty EA, Nicholls JM, Peiris JS, Mason RJ, Chan MC: Viral replication and innate host responses in primary human alveolar epithelial cells and alveolar macrophages infected with influenza H5N1 and H1N1 viruses. J Virol 2011, 85:6844-6855.
18. Korteweg C, Gu J: Pathology, molecular biology, and pathogenesis of avian influenza A (H5N1) infection in humans. Am J Pathol 2008, 172:1155-1170. (Pubitemid 351671530)
19. van Riel D, Leijten LM, van der Eerden M, Hoogsteden HC, Boven LA, Lambrecht BN, Osterhaus AD, Kuiken T: Highly pathogenic avian influenza virus H5N1 infects alveolar macrophages without virus production or excessive TNF-alpha induction. PLoS Pathog 2011, 7:e1002099.
20. Childs RA, Palma AS, Wharton S, Matrosovich T, Liu Y, Chai W, Campanero-Rhodes MA, Zhang Y, Eickmann M, Kiso M et al.: Receptor-binding specificity of pandemic influenza A (H1N1) 2009 virus determined by carbohydrate microarray. Nat Biotechnol 2009, 27:797-799.
21. Itoh Y, Shinya K, Kiso M, Watanabe T, Sakoda Y, Hatta M, Muramoto Y, Tamura D, Sakai-Tagawa Y, Noda T et al.: In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. Nature 2009, 460:1021-1025.
22. Munster VJ, de Wit E, van den Brand JM, Herfst S, Schrauwen EJ, Bestebroer TM, van de Vijver D, Boucher CA, Koopmans M, Rimmelzwaan GF et al.: Pathogenesis and transmission of swine-origin 2009 A(H1N1) influenza virus in ferrets. Science 2009, 325:481-483.
23. van den Brand JM, Stittelaar KJ, van Amerongen G, Rimmelzwaan GF, Simon J, de Wit E, Munster V, Bestebroer T, Fouchier RA, Kuiken T et al.: Severity of pneumonia due to new H1N1 influenza virus in ferrets is intermediate between that due to seasonal H1N1 virus and highly pathogenic avian influenza H5N1 virus. J Infect Dis 2010, 201:993-999. By quantifying virus antigen expression at different levels of the respiratory tract, this article shows that variation in virulence among influenza viruses is correlated to the localization of infection in the respiratory tract.
24. Shieh WJ, Blau DM, Denison AM, Deleon-Carnes M, Adem P, Bhatnagar J, Sumner J, Liu L, Patel M, Batten B et al.: 2009 pandemic influenza A (H1N1): pathology and pathogenesis of 100 fatal cases in the United States. Am J Pathol 2010, 177:166-175.
25. Guarner J, Paddock CD, Shieh WJ, Packard MM, Patel M, Montague JL, Uyeki TM, Bhat N, Balish A, Lindstrom S et al.: Histopathologic and immunohistochemical features of fatal influenza virus infection in children during the 2003-2004 season. Clin Infect Dis 2006, 43:132-140.
26. van Riel D, van den Brand JM, Munster VJ, Besteboer TM, Fouchier RA, Osterhaus AD, Kuiken T: Pathology and virus distribution in chickens naturally infected with highly pathogenic avian influenza A virus (H7N7) During the 2003 outbreak in The Netherlands. Vet Pathol 2009, 46:971-976.
27. Kuiken T, van den Brand J, van Riel D, Pantin-Jackwood M, Swayne DE: Comparative pathology of select agent influenza a virus infections. Vet Pathol 2010, 47:893-914.
28. Reperant LA, Rimmelzwaan GF, Kuiken T: Avian influenza viruses in mammals. Rev Sci Technol 2009, 28:137-159.
29. Ocana-Macchi M, Bel M, Guzylack-Piriou L, Ruggli N, Liniger M, McCullough KC, Sakoda Y, Isoda N, Matrosovich M, Summerfield A: Hemagglutinin-dependent tropism of H5N1 avian influenza virus for human endothelial cells. J Virol 2009, 83:12947-12955.
30. Zeng H, Pappas C, Belser JA, Houser KV, Zhong W, Wadford DA, Stevens T, Balczon R, Katz JM, Tumpey TM: Human pulmonary microvascular endothelial cells support productive replication of highly pathogenic avian influenza viruses: possible involvement in the pathogenesis of human H5N1 virus infection. J Virol 2012, 86:667-678.
31. Baskin CR, Bielefeldt-Ohmann H, Tumpey TM, Sabourin PJ, Long JP, Garcia-Sastre A, Tolnay AE, Albrecht R, Pyles JA, Olson PH et al.: Early and sustained innate immune response defines pathology and death in nonhuman primates infected by highly pathogenic influenza virus. Proc Natl Acad Sci U S A 2009, 106:3455-3460.
32. Rimmelzwaan GF, van Riel D, Baars M, Bestebroer TM, van Amerongen G, Fouchier RA, Osterhaus AD, Kuiken T: Influenza A virus (H5N1) infection in cats causes systemic disease with potential novel routes of virus spread within and between hosts. Am J Pathol 2006, 168:176-183 quiz 364.
33. Reperant LA, van de Bildt MW, van Amerongen G, Leijten LM, Watson S, Palser A, Kellam P, Eissens AC, Frijlink HW, Osterhaus AD et al.: Marked endotheliotropism of highly pathogenic avian influenza virus H5N1 following intestinal inoculation in cats. J Virol 2012, 86:1158-1165. This article shows that intra-intestinal inoculation of HPAI H5N1 virus changes its tropism from epithelial cells to endothelial cells. It is the first article to demonstrate widespread endotheliotropism of influenza virus in mammals.
34. Teijaro JR, Walsh KB, Cahalan S, Fremgen DM, Roberts E, Scott F, Martinborough E, Peach R, Oldstone MB, Rosen H: Endothelial cells are central orchestrators of cytokine amplification during influenza virus infection. Cell 2011, 146:980-991. This article implicates a role for endothelial cells through S1P1 signalling in orchestrating immune cell infiltration and cytokine production.
35. Garcia-Sastre A: Induction and evasion of type I interferon responses by influenza viruses. Virus Res 2011, 162:12-18.
36. Kreijtz JH, Fouchier RA, Rimmelzwaan GF: Immune responses to influenza virus infection. Virus Res 2011, 162:19-30.
37. Hancock K, Veguilla V, Lu X, Zhong W, Butler EN, Sun H, Liu F, Dong L, DeVos JR, Gargiullo PM et al.: Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus. N Engl J Med 2009, 361:1945-1952.
38. Smith DJ, Lapedes AS, de Jong JC, Bestebroer TM, Rimmelzwaan GF, Osterhaus AD, Fouchier RA: Mapping the antigenic and genetic evolution of influenza virus. Science 2004, 305:371-376. (Pubitemid 38938148)
39. Grebe KM, Yewdell JW, Bennink JR: Heterosubtypic immunity to influenza A virus: where do we stand? Microbes Infect 2008, 10:1024-1029.
40. Bodewes R, Kreijtz JH, Geelhoed-Mieras MM, van Amerongen G, Verburgh RJ, van Trierum SE, Kuiken T, Fouchier RA, Osterhaus AD, Rimmelzwaan GF: Vaccination against seasonal influenza A/H3N2 virus reduces the induction of heterosubtypic immunity against influenza A/H5N1 virus infection in ferrets. J Virol 2011, 85:2695-2702.
41. Flynn KJ, Belz GT, Altman JD, Ahmed R, Woodland DL, Doherty PC: Virus-specific CD8+ T cells in primary and secondary influenza pneumonia. Immunity 1998, 8:683-691. (Pubitemid 28294515)
42. Kreijtz JH, Bodewes R, van Amerongen G, Kuiken T, Fouchier RA, Osterhaus AD, Rimmelzwaan GF: Primary influenza A virus infection induces cross-protective immunity against a lethal infection with a heterosubtypic virus strain in mice. Vaccine 2007, 25:612-620. (Pubitemid 44856111)
43. Kreijtz JH, Bodewes R, van den Brand JM, de Mutsert G, Baas C, van Amerongen G, Fouchier RA, Osterhaus AD, Rimmelzwaan GF: Infection of mice with a human influenza A/H3N2 virus induces protective immunity against lethal infection with influenza A/ H5N1 virus. Vaccine 2009, 27:4983-4989.
44. O'Neill E, Krauss SL, Riberdy JM, Webster RG, Woodland DL: Heterologous protection against lethal A/HongKong/156/97 (H5N1) influenza virus infection in C57BL/6 mice. J Gen Virol 2000, 81:2689-2696.
45. Schulman JL, Kilbourne ED: Induction of partial specific heterotypic immunity in mice by a single infection with influenza a virus. J Bacteriol 1965, 89:170-174.
46. Seo SH, Peiris M, Webster RG: Protective cross-reactive cellular immunity to lethal A/Goose/Guangdong/1/96-like H5N1 influenza virus is correlated with the proportion of pulmonary CD8(+) T cells expressing gamma interferon. J Virol 2002, 76:4886-4890. (Pubitemid 34441694)
47. Hillaire ML, van Trierum SE, Kreijtz JH, Bodewes R, Geelhoed- Mieras MM, Nieuwkoop NJ, Fouchier RA, Kuiken T, Osterhaus AD, Rimmelzwaan GF: Cross-protective immunity against influenza pH1N1 2009 viruses induced by seasonal influenza A (H3N2) virus is mediated by virus-specific T-cells. J Gen Virol 2011, 92:2339-2349.
48. Jameson J, Cruz J, Terajima M, Ennis FA: Human CD8+ and CD4+ T lymphocyte memory to influenza A viruses of swine and avian species. J Immunol 1999, 162:7578-7583. (Pubitemid 29277740)
49. Kreijtz JH, de Mutsert G, van Baalen CA, Fouchier RA, Osterhaus AD, Rimmelzwaan GF: Cross-recognition of avian H5N1 influenza virus by human cytotoxic T-lymphocyte populations directed to human influenza A virus. J Virol 2008, 82:5161-5166. (Pubitemid 351705225)
50. Lee LY, Ha do LA, Simmons C, de Jong MD, Chau NV, Schumacher R, Peng YC, McMichael AJ, Farrar JJ, Smith GL et al.: Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals. J Clin Invest 2008, 118:3478-3490.
51. Scheible K, Zhang G, Baer J, Azadniv M, Lambert K, Pryhuber G, Treanor JJ, Topham DJ: CD8+ T cell immunity to 2009 pandemic and seasonal H1N1 influenza viruses. Vaccine 2011, 29:2159- 2168.
52. Tu W, Mao H, Zheng J, Liu Y, Chiu SS, Qin G, Chan PL, Lam KT, Guan J, Zhang L et al.: Cytotoxic T lymphocytes established by seasonal human influenza cross-react against 2009 pandemic H1N1 influenza virus. J Virol 2010, 84:6527-6535.
53. McMichael AJ, Gotch FM, Noble GR, Beare PA: Cytotoxic T-cell immunity to influenza. N Engl J Med 1983, 309:13-17. (Pubitemid 13062888)
54. Epstein SL: Prior H1N1 influenza infection and susceptibility of Cleveland family study participants during the H2N2 pandemic of 1957: an experiment of nature. J Infect Dis 2006, 193:49-53.
55. Fodor E, Devenish L, Engelhardt OG, Palese P, Brownlee GG, Garcia-Sastre A: Rescue of influenza A virus from recombinant DNA. J Virol 1999, 73:9679-9682. (Pubitemid 29487131)
56. Hoffmann E, Neumann G, Kawaoka Y, Hobom G, Webster RG: A DNA transfection system for generation of influenza A virus from eight plasmids. Proc Natl Acad Sci U S A 2000, 97:6108-6113. (Pubitemid 30367531)
57. Neumann G, Watanabe T, Ito H, Watanabe S, Goto H, Gao P, Hughes M, Perez DR, Donis R, Hoffmann E et al.: Generation of influenza A viruses entirely from cloned cDNAs. Proc Natl Acad Sci U S A 1999, 96:9345-9350. (Pubitemid 29374757)
58. Bosch FX, Garten W, Klenk HD, Rott R: Proteolytic cleavage of influenza virus hemagglutinins: primary structure of the connecting peptide between HA1 and HA2 determines proteolytic cleavability and pathogenicity of Avian influenza viruses. Virology 1981, 113:725-735. (Pubitemid 11056361)
59. Kawaoka Y, Webster RG: Sequence requirements for cleavage activation of influenza virus hemagglutinin expressed in mammalian cells. Proc Natl Acad Sci U S A 1988, 85:324-328.
60. Rimmelzwaan GF, Kuiken T, van Amerongen G, Bestebroer TM, Fouchier RA, Osterhaus AD: Pathogenesis of influenza A (H5N1) virus infection in a primate model. J Virol 2001, 75:6687-6691. (Pubitemid 32578188)
61. Hatta M, Gao P, Halfmann P, Kawaoka Y: Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science 2001, 293:1840-1842. (Pubitemid 32845783)
62. Rogers GN, Paulson JC: Receptor determinants of human and animal influenza virus isolates: differences in receptor specificity of the H3 hemagglutinin based on species of origin. Virology 1983, 127:361-373. (Pubitemid 13026446)
63. Connor RJ, Kawaoka Y, Webster RG, Paulson JC: Receptor specificity in human, avian, and equine H2 and H3 influenza virus isolates. Virology 1994, 205:17-23. (Pubitemid 24360586)
64. Glaser L, Stevens J, Zamarin D, Wilson IA, Garcia-Sastre A, Tumpey TM, Basler CF, Taubenberger JK, Palese P: A single amino acid substitution in 1918 influenza virus hemagglutinin changes receptor binding specificity. J Virol 2005, 79:11533-11536. (Pubitemid 41170697)
65. Matrosovich M, Tuzikov A, Bovin N, Gambaryan A, Klimov A, Castrucci MR, Donatelli I, Kawaoka Y: Early alterations of the receptor-binding properties of H1, H2, and H3 avian influenza virus hemagglutinins after their introduction into mammals. J Virol 2000, 74:8502-8512. (Pubitemid 30666701)
66. Stevens J, Corper AL, Basler CF, Taubenberger JK, Palese P, Wilson IA: Structure of the uncleaved human H1 hemagglutinin from the extinct 1918 influenza virus. Science 2004, 303:1866-1870. (Pubitemid 38374878)
67. Auewarakul P, Suptawiwat O, Kongchanagul A, Sangma C, Suzuki Y, Ungchusak K, Louisirirotchanakul S, Lerdsamran H, Pooruk P, Thitithanyanont A et al.: An avian influenza H5N1 virus that binds to a human-type receptor. J Virol 2007, 81:9950-9955. (Pubitemid 350067698)
68. Chutinimitkul S, van Riel D, Munster VJ, van den Brand JM, Rimmelzwaan GF, Kuiken T, Osterhaus AD, Fouchier RA, de Wit E: In vitro assessment of attachment pattern and replication efficiency of H5N1 influenza A viruses with altered receptor specificity. J Virol 2010, 84:6825-6833.
69. Gambaryan A, Tuzikov A, Pazynina G, Bovin N, Balish A, Klimov A: Evolution of the receptor binding phenotype of influenza A (H5) viruses. Virology 2006, 344:432-438. (Pubitemid 43049630)
70. Yamada S, Suzuki Y, Suzuki T, Le MQ, Nidom CA, Sakai- Tagawa Y, Muramoto Y, Ito M, Kiso M, Horimoto T et al.: Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors. Nature 2006, 444:378-382. (Pubitemid 44764114)
71. Stevens J, Blixt O, Tumpey TM, Taubenberger JK, Paulson JC, Wilson IA: Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus. Science 2006, 312:404-410.
72. Chen H, Bright RA, Subbarao K, Smith C, Cox NJ, Katz JM, Matsuoka Y: Polygenic virulence factors involved in pathogenesis of 1997 Hong Kong H5N1 influenza viruses in mice. Virus Res 2007, 128:159-163. (Pubitemid 47242890)
73. de Wit E, Munster VJ, van Riel D, Beyer WE, Rimmelzwaan GF, Kuiken T, Osterhaus AD, Fouchier RA: Molecular determinants of adaptation of highly pathogenic avian influenza H7N7 viruses to efficient replication in the human host. J Virol 2010, 84:1597-1606. This article gives a comprehensive analysis of the viral molecular determinants of adaptation of HPAI H7N7 virus to infection in humans.
74. Baum LG, Paulson JC: The N2 neuraminidase of human influenza virus has acquired a substrate specificity complementary to the hemagglutinin receptor specificity. Virology 1991, 180:10-15.
75. Wagner R, Matrosovich M, Klenk HD: Functional balance between haemagglutinin and neuraminidase in influenza virus infections. Rev Med Virol 2002, 12:159-166. (Pubitemid 34516947)
76. Tumpey TM, Basler CF, Aguilar PV, Zeng H, Solorzano A, Swayne DE, Cox NJ, Katz JM, Taubenberger JK, Palese P et al.: Characterization of the reconstructed 1918 Spanish influenza pandemic virus. Science 2005, 310:77-80. (Pubitemid 41434537)
77. Subbarao EK, London W, Murphy BR: A single amino acid in the PB2 gene of influenza A virus is a determinant of host range. J Virol 1993, 67:1761-1764. (Pubitemid 23088345)
78. Li Z, Chen H, Jiao P, Deng G, Tian G, Li Y, Hoffmann E, Webster RG, Matsuoka Y, Yu K: Molecular basis of replication of duck H5N1 influenza viruses in a mammalian mouse model. J Virol 2005, 79:12058-12064. (Pubitemid 41279322)
79. Mase M, Tanimura N, Imada T, Okamatsu M, Tsukamoto K, Yamaguchi S: Recent H5N1 avian influenza A virus increases rapidly in virulence to mice after a single passage in mice. J Gen Virol 2006, 87:3655-3659. (Pubitemid 44816999)
80. Munster VJ, de Wit E, van Riel D, Beyer WE, Rimmelzwaan GF, Osterhaus AD, Kuiken T, Fouchier RA: The molecular basis of the pathogenicity of the Dutch highly pathogenic human influenza A H7N7 viruses. J Infect Dis 2007, 196:258-265. (Pubitemid 47047465)
81. Steel J, Lowen AC, 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:e1000252.
82. Gabriel G, Herwig A, Klenk HD: Interaction of polymerase subunit PB2 and NP with importin alpha1 is a determinant of host range of influenza A virus. PLoS Pathog 2008, 4:e11.
83. Gabriel G, Dauber B, Wolff T, Planz O, Klenk HD, Stech J: The viral polymerase mediates adaptation of an avian influenza virus to a mammalian host. Proc Natl Acad Sci U S A 2005, 102:18590-18595. (Pubitemid 43011270)
84. de Jong MD, Simmons CP, Thanh TT, Hien VM, Smith GJ, Chau TN, Hoang DM, Chau NV, Khanh TH, Dong VC et al.: Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nat Med 2006, 12:1203-1207. (Pubitemid 44527358)
85. Mehle A, Doudna JA: Adaptive strategies of the influenza virus polymerase for replication in humans. Proc Natl Acad Sci U S A 2009, 106:21312-21316.
86. Herfst S, Chutinimitkul S, Ye J, de Wit E, Munster VJ, Schrauwen EJ, Bestebroer TM, Jonges M, Meijer A, Koopmans M et al.: Introduction of virulence markers in PB2 of pandemic swine-origin influenza virus does not result in enhanced virulence or transmission. J Virol 2010, 84:3752-3758.
87. Salomon R, Franks J, Govorkova EA, Ilyushina NA, Yen HL, Hulse- Post DJ, Humberd J, Trichet M, Rehg JE, Webby RJ et al.: The polymerase complex genes contribute to the high virulence of the human H5N1 influenza virus isolate A/Vietnam/1203/04. J Exp Med 2006, 203:689-697.
88. Chen GW, Chang SC, Mok CK, Lo YL, Kung YN, Huang JH, Shih YH, Wang JY, Chiang C, Chen CJ et al.: Genomic signatures of human versus avian influenza A viruses. Emerg Infect Dis 2006, 12:1353-1360. (Pubitemid 44455211)
89. Finkelstein DB, Mukatira S, Mehta PK, Obenauer JC, Su X, Webster RG, Naeve CW: Persistent host markers in pandemic and H5N1 influenza viruses. J Virol 2007, 81:10292-10299. (Pubitemid 47463304)
90. Seo SH, Hoffmann E, Webster RG: Lethal H5N1 influenza viruses escape host anti-viral cytokine responses. Nat Med 2002, 8:950-954. (Pubitemid 35033698)
91. Jiao P, Tian G, Li Y, Deng G, Jiang Y, Liu C, Liu W, Bu Z, Kawaoka Y, Chen H: A single-amino-acid substitution in the NS1 protein changes the pathogenicity of H5N1 avian influenza viruses in mice. J Virol 2008, 82:1146-1154.
92. Twu KY, Kuo RL, Marklund J, Krug RM: The H5N1 influenza virus NS genes selected after 1998 enhance virus replication in mammalian cells. J Virol 2007, 81:8112-8121. (Pubitemid 47101497)
93. Jackson D, Hossain MJ, Hickman D, Perez DR, Lamb RA: A new influenza virus virulence determinant: the NS1 protein four C-terminal residues modulate pathogenicity. Proc Natl Acad Sci U S A 2008, 105:4381-4386. (Pubitemid 351754389)
94. Hale BG, Steel J, Manicassamy B, Medina RA, Ye J, Hickman D, Lowen AC, Perez DR, Garcia-Sastre A: Mutations in the NS1 C-terminal tail do not enhance replication or virulence of the 2009 pandemic H1N1 influenza A virus. J Gen Virol 2010, 91:1737-1742.
95. Ozawa M, Basnet S, Burley LM, 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, 85:4596-4601.
96. Conenello GM, Zamarin D, Perrone LA, Tumpey T, Palese P: A single mutation in the PB1-F2 of H5N1 (HK/97) and 1918 influenza A viruses contributes to increased virulence. PLoS Pathog 2007, 3:1414-1421. (Pubitemid 350085606)
97. Hai R, Schmolke M, Varga ZT, Manicassamy B, Wang TT, Belser JA, Pearce MB, Garcia-Sastre A, Tumpey TM, Palese P: PB1-F2 expression by the 2009 pandemic H1N1 influenza virus has minimal impact on virulence in animal models. J Virol 2010, 84:4442-4450.
98. Cheung CY, Poon LL, Lau AS, Luk W, Lau YL, Shortridge KF, Gordon S, Guan Y, Peiris JS: Induction of proinflammatory cytokines in human macrophages by influenza A (H5N1) viruses: a mechanism for the unusual severity of human disease? Lancet 2002, 360:1831-1837. (Pubitemid 35449422)
99. Kobasa D, Takada A, Shinya K, Hatta M, Halfmann P, Theriault S, Suzuki H, Nishimura H, Mitamura K, Sugaya N et al.: Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus. Nature 2004, 431:703-707. (Pubitemid 39382618)
100. Billharz R, Zeng H, Proll SC, Korth MJ, Lederer S, Albrecht R, Goodman AG, Rosenzweig E, Tumpey TM, Garcia-Sastre A et al.: The NS1 protein of the 1918 pandemic influenza virus blocks host interferon and lipid metabolism pathways. J Virol 2009, 83:10557-10570.
101. Tumpey TM, Garcia-Sastre A, Taubenberger JK, Palese P, Swayne DE, Pantin-Jackwood MJ, Schultz-Cherry S, Solorzano A, Van Rooijen N, Katz JM et al.: Pathogenicity of influenza viruses with genes from the 1918 pandemic virus: functional roles of alveolar macrophages and neutrophils in limiting virus replication and mortality in mice. J Virol 2005, 79:14933-14944. (Pubitemid 41636290)
102. McAuley JL, Hornung F, Boyd KL, Smith AM, McKeon R, Bennink J, Yewdell JW, McCullers JA: Expression of the 1918 influenza A virus PB1-F2 enhances the pathogenesis of viral and secondary bacterial pneumonia. Cell Host Microbe 2007, 2:240-249. (Pubitemid 47500821)
103. Rogers GN, Paulson JC, Daniels RS, Skehel JJ, Wilson IA, Wiley DC: Single amino acid substitutions in influenza haemagglutinin change receptor binding specificity. Nature 1983, 304:76-78. (Pubitemid 13063111)
104. Matrosovich MN, Matrosovich TY, Gray T, Roberts NA, Klenk HD: Human and avian influenza viruses target different cell types in cultures of human airway epithelium. Proc Natl Acad Sci U S A 2004, 101:4620-4624. (Pubitemid 38437460)
105. Hale BG, Albrecht RA, Garcia-Sastre A: Innate immune evasion strategies of influenza viruses. Future Microbiol 2010, 5:23-41.
106. Varga ZT, Palese P: The influenza A virus protein PB1-F2: Killing two birds with one stone? Virulence 2011, 2:542-546.
107. Goto H, Wells K, Takada A, Kawaoka Y: Plasminogen-binding activity of neuraminidase determines the pathogenicity of influenza A virus. J Virol 2001, 75:9297-9301. (Pubitemid 32851933)
108. LeBouder F, Lina B, Rimmelzwaan GF, Riteau B: Plasminogen promotes influenza A virus replication through an annexin 2- dependent pathway in the absence of neuraminidase. J Gen Virol 2010, 91:2753-2761.
109. Garcia CC, Russo RC, Guabiraba R, Fagundes CT, Polidoro RB, Tavares LP, Salgado AP, Cassali GD, Sousa LP, Machado AV et al.: Platelet-activating factor receptor plays a role in lung injury and death caused by Influenza A in mice. PLoS Pathog 2010, 6:e1001171.
110. Le Goffic R, Balloy V, Lagranderie M, Alexopoulou L, Escriou N, Flavell R, Chignard M, Si-Tahar M: Detrimental contribution of the Toll-like receptor (TLR)3 to influenza A virus-induced acute pneumonia. PLoS Pathog 2006, 2:e53.
111. Carlson CM, Turpin EA, Moser LA, O'Brien KB, Cline TD, Jones JC, Tumpey TM, Katz JM, Kelley LA, Gauldie J et al.: Transforming growth factor-beta: activation by neuraminidase and role in highly pathogenic H5N1 influenza pathogenesis. PLoS Pathog 2010, 6:e1001136.
112. LeBouder F, Khoufache K, Menier C, Mandouri Y, Keffous M, Lejal N, Krawice-Radanne I, Carosella ED, Rouas-Freiss N, Riteau B: Immunosuppressive HLA-G molecule is upregulated in alveolar epithelial cells after influenza A virus infection. Hum Immunol 2009, 70:1016-1019.
113. Sun J, Madan R, Karp CL, Braciale TJ: Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10. Nat Med 2009, 15:277-284.
114. Khoufache K, LeBouder F, Morello E, Laurent F, Riffault S, Andrade-Gordon P, Boullier S, Rousset P, Vergnolle N, Riteau B: Protective role for protease-activated receptor-2 against influenza virus pathogenesis via an IFN-gamma-dependent pathway. J Immunol 2009, 182:7795-7802. This study is the first to demonstrate the role of protease-activated receptor in influenza pathogenesis. Small peptides activating those receptors have promising therapeutic effect by inhibiting lung inflammation induced by influenza virus infection.
115. Snelgrove RJ, Goulding J, Didierlaurent AM, Lyonga D, Vekaria S, Edwards L, Gwyer E, Sedgwick JD, Barclay AN, Hussell T: A critical function for CD200 in lung immune homeostasis and the severity of influenza infection. Nat Immunol 2008, 9:1074-1083. This study shows that CD200 deficiency increased lung inflammation induced by influenza virus infections. In contrast, CD200R agonists ameliorated inflammation and protected mice from severe disease caused by influenza.
116. Rygiel TP, Rijkers ES, de Ruiter T, Stolte EH, van der Valk M, Rimmelzwaan GF, Boon L, van Loon AM, Coenjaerts FE, Hoek RM et al.: Lack of CD200 enhances pathological T cell responses during influenza infection. J Immunol 2009, 183:1990-1996.
117. Walsh KB, Teijaro JR, Wilker PR, Jatzek A, Fremgen DM, Das SC, Watanabe T, Hatta M, Shinya K, Suresh M et al.: Suppression of cytokine storm with a sphingosine analog provides protection against pathogenic influenza virus. Proc Natl Acad Sci U S A 2011, 108:12018-12023.