1887

Abstract

Ducks, the reservoir host, are generally permissive to influenza A virus infection without disease symptoms. This natural ecology was upset by the emergence of H5N1 strains, which can kill ducks. To better understand host–virus interactions in the reservoir host, and influenza strain-specific molecular contributions to virulence, we infected White Pekin ducks with three similar H5N1 viruses, with known differences in pathogenicity and replication rate. We quantified viral replication and innate immune gene activation by qPCR, in lung and spleen tissues, isolated on each of the first 3 days of infection. The three viruses replicated well, as measured by accumulation of matrix gene transcript, and viral load declined over time in the spleen. The ducks produced rapid, but temporally limited, IFN and cytokine responses, peaking on the first day post-infection. IFN and proinflammatory cytokine gene induction were greater in response to infection with the more lethal viruses, compared to an attenuated strain. We conclude that a well-regulated IFN response, with the ability to overcome early viral immune inhibition, without hyperinflammation, contributes to the ability of ducks to survive H5N1 influenza replication in their airways, and yet clear systemic infection and limit disease.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.001015
2018-04-01
2024-04-23
Loading full text...

Full text loading...

/deliver/fulltext/jgv/99/4/464.html?itemId=/content/journal/jgv/10.1099/jgv.0.001015&mimeType=html&fmt=ahah

References

  1. Molinari NA, Ortega-Sanchez IR, Messonnier ML, Thompson WW, Wortley PM et al. The annual impact of seasonal influenza in the US: measuring disease burden and costs. Vaccine 2007; 25:5086–5096 [View Article][PubMed]
    [Google Scholar]
  2. Rajao DS, Anderson TK, Gauger PC, Vincent AL. Pathogenesis and vaccination of influenza A virus in swine. Curr Top Microbiol Immunol 2014; 385:307–326 [View Article][PubMed]
    [Google Scholar]
  3. Klepser ME. Socioeconomic impact of seasonal (epidemic) influenza and the role of over-the-counter medicines. Drugs 2014; 74:1467–1479 [View Article][PubMed]
    [Google Scholar]
  4. Preaud E, Durand L, Macabeo B, Farkas N, Sloesen B et al. Annual public health and economic benefits of seasonal influenza vaccination: a European estimate. BMC Public Health 2014; 14:813 [View Article][PubMed]
    [Google Scholar]
  5. Taubenberger JK, Kash JC. Influenza virus evolution, host adaptation, and pandemic formation. Cell Host Microbe 2010; 7:440–451 [View Article][PubMed]
    [Google Scholar]
  6. Webster RG, Bean WJ, Gorman OT, Chambers TM, Kawaoka Y. Evolution and ecology of influenza A viruses. Microbiol Rev 1992; 56:152–179[PubMed]
    [Google Scholar]
  7. Guan Y, Shortridge KF, Krauss S, Webster RG. Molecular characterization of H9N2 influenza viruses: were they the donors of the "internal" genes of H5N1 viruses in Hong Kong?. Proc Natl Acad Sci USA 1999; 96:9363–9367 [View Article][PubMed]
    [Google Scholar]
  8. Kageyama T, Fujisaki S, Takashita E, Xu H, Yamada S et al. Genetic analysis of novel avian A(H7N9) influenza viruses isolated from patients in China, February to April 2013. Euro Surveill 2013; 18:20453[PubMed]
    [Google Scholar]
  9. Liu D, Shi W, Shi Y, Wang D, Xiao H et al. Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: phylogenetic, structural, and coalescent analyses. Lancet 2013; 381:1926–1932 [View Article][PubMed]
    [Google Scholar]
  10. Alexander DJ, Parsons G, Manvell RJ. Experimental assessment of the pathogenicity of eight avian influenza A viruses of H5 subtype for chickens, turkeys, ducks and quail. Avian Pathol 1986; 15:647–662 [View Article][PubMed]
    [Google Scholar]
  11. Cooley AJ, van Campen H, Philpott MS, Easterday BC, Hinshaw VS. Pathological lesions in the lungs of ducks infected with influenza A viruses. Vet Pathol 1989; 26:1–5 [View Article][PubMed]
    [Google Scholar]
  12. Laudert EA, Sivanandan V, Halvorson DA. Effect of intravenous inoculation of avian influenza virus on reproduction and growth in mallard ducks. J Wildl Dis 1993; 29:523–526 [View Article][PubMed]
    [Google Scholar]
  13. Shortridge KF, Zhou NN, Guan Y, Gao P, Ito T et al. Characterization of avian H5N1 influenza viruses from poultry in Hong Kong. Virology 1998; 252:331–342 [View Article][PubMed]
    [Google Scholar]
  14. Kim JK, Negovetich NJ, Forrest HL, Webster RG. Ducks: the "Trojan horses" of H5N1 influenza. Influenza Other Respir Viruses 2009; 3:121–128 [View Article][PubMed]
    [Google Scholar]
  15. Kida H, Yanagawa R, Matsuoka Y. Duck influenza lacking evidence of disease signs and immune response. Infect Immun 1980; 30:547–553[PubMed]
    [Google Scholar]
  16. Sturm-Ramirez KM, Hulse-Post DJ, Govorkova EA, Humberd J, Seiler P et al. Are ducks contributing to the endemicity of highly pathogenic H5N1 influenza virus in Asia?. J Virol 2005; 79:11269–11279 [View Article][PubMed]
    [Google Scholar]
  17. Vanderven HA, Petkau K, Ryan-Jean KE, Aldridge JR, Webster RG et al. Avian influenza rapidly induces antiviral genes in duck lung and intestine. Mol Immunol 2012; 51:316–324 [View Article][PubMed]
    [Google Scholar]
  18. Pantin-Jackwood MJ, Costa-Hurtado M, Shepherd E, Dejesus E, Smith D et al. Pathogenicity and transmission of H5 and H7 highly pathogenic avian influenza viruses in mallards. J Virol 2016; 90:9967–9982 [View Article][PubMed]
    [Google Scholar]
  19. Burggraaf S, Karpala AJ, Bingham J, Lowther S, Selleck P et al. H5N1 infection causes rapid mortality and high cytokine levels in chickens compared to ducks. Virus Res 2014; 185:23–31 [View Article][PubMed]
    [Google Scholar]
  20. Teijaro JR, Walsh KB, Rice S, Rosen H, Oldstone MB. Mapping the innate signaling cascade essential for cytokine storm during influenza virus infection. Proc Natl Acad Sci USA 2014; 111:3799–3804 [View Article][PubMed]
    [Google Scholar]
  21. Teijaro JR, Walsh KB, Cahalan S, Fremgen DM, Roberts E et al. Endothelial cells are central orchestrators of cytokine amplification during influenza virus infection. Cell 2011; 146:980–991 [View Article][PubMed]
    [Google Scholar]
  22. Yuen KY, Wong SS. Human infection by avian influenza A H5N1. Hong Kong Med J 2005; 11:189–199[PubMed]
    [Google Scholar]
  23. Peiris JS, Yu WC, Leung CW, Cheung CY, Ng WF et al. Re-emergence of fatal human influenza A subtype H5N1 disease. Lancet 2004; 363:617–619 [View Article][PubMed]
    [Google Scholar]
  24. Cheung CY, Poon LL, Lau AS, Luk W, Lau YL et al. 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 [View Article][PubMed]
    [Google Scholar]
  25. Liang QL, Luo J, Zhou K, Dong JX, He HX. Immune-related gene expression in response to H5N1 avian influenza virus infection in chicken and duck embryonic fibroblasts. Mol Immunol 2011; 48:924–930 [View Article][PubMed]
    [Google Scholar]
  26. Wei L, Jiao P, Song Y, Cao L, Yuan R et al. Host immune responses of ducks infected with H5N1 highly pathogenic avian influenza viruses of different pathogenicities. Vet Microbiol 2013; 166:386–393 [View Article][PubMed]
    [Google Scholar]
  27. Govorkova EA, Rehg JE, Krauss S, Yen HL, Guan Y et al. Lethality to ferrets of H5N1 influenza viruses isolated from humans and poultry in 2004. J Virol 2005; 79:2191–2198 [View Article][PubMed]
    [Google Scholar]
  28. Songserm T, Jam-On R, Sae-Heng N, Meemak N, Hulse-Post DJ et al. Domestic ducks and H5N1 influenza epidemic, Thailand. Emerg Infect Dis 2006; 12:575–581 [View Article][PubMed]
    [Google Scholar]
  29. Salomon R, Franks J, Govorkova EA, Ilyushina NA, Yen HL 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 [View Article][PubMed]
    [Google Scholar]
  30. Hulse-Post DJ, Franks J, Boyd K, Salomon R, Hoffmann E et al. Molecular changes in the polymerase genes (PA and PB1) associated with high pathogenicity of H5N1 influenza virus in mallard ducks. J Virol 2007; 81:8515–8524 [View Article][PubMed]
    [Google Scholar]
  31. Marjuki H, Scholtissek C, Franks J, Negovetich NJ, Aldridge JR et al. Three amino acid changes in PB1-F2 of highly pathogenic H5N1 avian influenza virus affect pathogenicity in mallard ducks. Arch Virol 2010; 155:925–934 [View Article][PubMed]
    [Google Scholar]
  32. Weber-Gerlach M, Weber F. Standing on three legs: antiviral activities of RIG-I against influenza viruses. Curr Opin Immunol 2016; 42:71–75 [View Article][PubMed]
    [Google Scholar]
  33. Barber MR, Aldridge JR, Webster RG, Magor KE. Association of RIG-I with innate immunity of ducks to influenza. Proc Natl Acad Sci USA 2010; 107:5913–5918 [View Article][PubMed]
    [Google Scholar]
  34. Cagle C, To TL, Nguyen T, Wasilenko J, Adams SC et al. Pekin and Muscovy ducks respond differently to vaccination with a H5N1 highly pathogenic avian influenza (HPAI) commercial inactivated vaccine. Vaccine 2011; 29:6549–6557 [View Article][PubMed]
    [Google Scholar]
  35. Chen SN, Zou PF, Nie P. Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) in fish: current knowledge and future perspectives. Immunology 2017; 151:16–25 [View Article][PubMed]
    [Google Scholar]
  36. Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T et al. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol 2004; 5:730–737 [View Article][PubMed]
    [Google Scholar]
  37. Kim KS, Jung H, Shin IK, Choi BR, Kim DH. Induction of interleukin-1 beta (IL-1β) is a critical component of lung inflammation during influenza A (H1N1) virus infection. J Med Virol 2015; 87:1104–1112 [View Article][PubMed]
    [Google Scholar]
  38. Kuribayashi S, Sakoda Y, Kawasaki T, Tanaka T, Yamamoto N et al. Excessive cytokine response to rapid proliferation of highly pathogenic avian influenza viruses leads to fatal systemic capillary leakage in chickens. PLoS One 2013; 8:e68375 [View Article][PubMed]
    [Google Scholar]
  39. Arimori Y, Nakamura R, Yamada H, Shibata K, Maeda N et al. Type I interferon limits influenza virus-induced acute lung injury by regulation of excessive inflammation in mice. Antiviral Res 2013; 99:230–237 [View Article][PubMed]
    [Google Scholar]
  40. Koerner I, Kochs G, Kalinke U, Weiss S, Staeheli P. Protective role of beta interferon in host defense against influenza A virus. J Virol 2007; 81:2025–2030 [View Article][PubMed]
    [Google Scholar]
  41. Loo YM, Fornek J, Crochet N, Bajwa G, Perwitasari O et al. Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. J Virol 2008; 82:335–345 [View Article][PubMed]
    [Google Scholar]
  42. Varga ZT, Ramos I, Hai R, Schmolke M, García-Sastre A et al. 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:e1002067 [View Article][PubMed]
    [Google Scholar]
  43. Hale BG, Randall RE, Ortín J, Jackson D. The multifunctional NS1 protein of influenza A viruses. J Gen Virol 2008; 89:2359–2376 [View Article][PubMed]
    [Google Scholar]
  44. Zielecki F, Semmler I, Kalthoff D, Voss D, Mauel S et al. Virulence determinants of avian H5N1 influenza A virus in mammalian and avian hosts: role of the C-terminal ESEV motif in the viral NS1 protein. J Virol 2010; 84:10708–10718 [View Article][PubMed]
    [Google Scholar]
  45. Li H, Bradley KC, Long JS, Frise R, Ashcroft JW et al. Internal genes of a highly pathogenic H5N1 influenza virus determine high viral replication in myeloid cells and severe outcome of infection in mice. PLoS Pathog 2018; 14:e1006821 [View Article][PubMed]
    [Google Scholar]
  46. Schat KA, Bingham J, Butler JM, Chen LM, Lowther S et al. Role of position 627 of PB2 and the multibasic cleavage site of the hemagglutinin in the virulence of H5N1 avian influenza virus in chickens and ducks. PLoS One 2012; 7:e30960 [View Article][PubMed]
    [Google Scholar]
  47. Karpala AJ, Bingham J, Schat KA, Chen LM, Donis RO et al. Highly pathogenic (H5N1) avian influenza induces an inflammatory T helper type 1 cytokine response in the chicken. J Interferon Cytokine Res 2011; 31:393–400 [View Article][PubMed]
    [Google Scholar]
  48. Abbas YM, Pichlmair A, Górna MW, Superti-Furga G, Nagar B. Structural basis for viral 5'-PPP-RNA recognition by human IFIT proteins. Nature 2013; 494:60–64 [View Article][PubMed]
    [Google Scholar]
  49. Zhu J, Ghosh A, Sarkar SN. OASL-a new player in controlling antiviral innate immunity. Curr Opin Virol 2015; 12:15–19 [View Article][PubMed]
    [Google Scholar]
  50. Zhu J, Zhang Y, Ghosh A, Cuevas RA, Forero A et al. Antiviral activity of human OASL protein is mediated by enhancing signaling of the RIG-I RNA sensor. Immunity 2014; 40:936–948 [View Article][PubMed]
    [Google Scholar]
  51. Tumpey TM, Szretter KJ, van Hoeven N, Katz JM, Kochs G et al. The Mx1 gene protects mice against the pandemic 1918 and highly lethal human H5N1 influenza viruses. J Virol 2007; 81:10818–10821 [View Article][PubMed]
    [Google Scholar]
  52. Horisberger MA, de Staritzky K. Expression and stability of the Mx protein in different tissues of mice, in response to interferon inducers or to influenza virus infection. J Interferon Res 1989; 9:583–590 [View Article][PubMed]
    [Google Scholar]
  53. Staeheli P, Pitossi F, Pavlovic J. Mx proteins: GTPases with antiviral activity. Trends Cell Biol 1993; 3:268–272 [View Article][PubMed]
    [Google Scholar]
  54. Bazzigher L, Schwarz A, Staeheli P. No enhanced influenza virus resistance of murine and avian cells expressing cloned duck Mx protein. Virology 1993; 195:100–112 [View Article][PubMed]
    [Google Scholar]
  55. Dillon D, Runstadler J. Mx gene diversity and influenza association among five wild dabbling duck species (Anas spp.) in Alaska. Infect Genet Evol 2010; 10:1085–1093 [View Article][PubMed]
    [Google Scholar]
  56. Guo XJ, Thomas PG. New fronts emerge in the influenza cytokine storm. Semin Immunopathol 2017; 39:541–550 [View Article][PubMed]
    [Google Scholar]
  57. 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 [View Article][PubMed]
    [Google Scholar]
  58. Tundup S, Kandasamy M, Perez JT, Mena N, Steel J et al. Endothelial cell tropism is a determinant of H5N1 pathogenesis in mammalian species. PLoS Pathog 2017; 13:e1006270 [View Article][PubMed]
    [Google Scholar]
  59. Uchida Y, Chaichoune K, Wiriyarat W, Watanabe C, Hayashi T et al. Molecular epidemiological analysis of highly pathogenic avian influenza H5N1 subtype isolated from poultry and wild bird in Thailand. Virus Res 2008; 138:70–80 [View Article][PubMed]
    [Google Scholar]
  60. Lipatov AS, Kwon YK, Sarmento LV, Lager KM, Spackman E et al. Domestic pigs have low susceptibility to H5N1 highly pathogenic avian influenza viruses. PLoS Pathog 2008; 4:e1000102 [View Article][PubMed]
    [Google Scholar]
  61. Pfeiffer J, Pantin-Jackwood M, To TL, Nguyen T, Suarez DL. Phylogenetic and biological characterization of highly pathogenic H5N1 avian influenza viruses (Vietnam 2005) in chickens and ducks. Virus Res 2009; 142:108–120 [View Article][PubMed]
    [Google Scholar]
  62. Sturm-Ramirez KM, Ellis T, Bousfield B, Bissett L, Dyrting K et al. Reemerging H5N1 influenza viruses in Hong Kong in 2002 are highly pathogenic to ducks. J Virol 2004; 78:4892–4901 [View Article][PubMed]
    [Google Scholar]
  63. Reed LD, Muench H. A simple method of estimating fifty percent endpoints. Am J Hyg 1938; 27:493–497
    [Google Scholar]
  64. Hirst GK. The quantitative determination of influenza virus and antibodies by means of red cell agglutination. J Exp Med 1942; 75:49–64 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.001015
Loading
/content/journal/jgv/10.1099/jgv.0.001015
Loading

Data & Media loading...

Supplements

Supplementary File 1

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error