1887

Abstract

Avian influenza is a significant economic burden on the poultry industry in geographical regions where it is enzootic. It also poses a public health concern when avian influenza subtypes infect humans, often with high mortality. Understanding viral genetic factors which positively contribute to influenza A virus (IAV) fitness – infectivity, spread and pathogenesis – is of great importance both for human and livestock health. PB1-F2 is a small accessory protein encoded by IAV and in mammalian hosts has been implicated in a wide range of functions that contribute to increased pathogenesis. In the avian host, the protein has been understudied despite high-level full-length conservation in avian IAV isolates, which is in contrast to the truncations of the PB1-F2 length frequently found in mammalian host isolates. Here we report that the presence of a full-length PB1-F2 protein, from a low pathogenicity H9N2 avian influenza virus, prolongs infectious virus shedding from directly inoculated chickens, thereby enhancing transmission of the virus by lengthening the transmission window to contact birds. As well as extending transmission, the presence of a full-length PB1-F2 suppresses pathogenicity evidenced by an increased minimum lethal dose in embryonated chicken eggs and increasing survival in directly infected birds when compared to a virus lacking an ORF for PB1-F2. We propose that there is a positive pressure to maintain a full-length functional PB1-F2 protein upon infection of avian hosts as it contributes to the effective transmission of IAV in the field.

Keyword(s): avian influenza , PB1-F2 and transmission
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2016-10-13
2019-10-14
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References

  1. Alexander D. J..( 2007;). An overview of the epidemiology of avian influenza. . Vaccine 25: 5637–5644. [CrossRef] [PubMed]
    [Google Scholar]
  2. Armesto M., Cavanagh D., Britton P..( 2009;). The replicase gene of avian coronavirus infectious bronchitis virus is a determinant of pathogenicity. . PLoS One 4:,e7384. [CrossRef] [PubMed]
    [Google Scholar]
  3. Breban R., Drake J. M., Stallknecht D. E., Rohani P..( 2009;). The role of environmental transmission in recurrent avian influenza epidemics. . PLoS Comput Biol 5:,e1000346. [CrossRef] [PubMed]
    [Google Scholar]
  4. Brown J. D., Swayne D. E., Cooper R. J., Burns R. E., Stallknecht D. E..( 2007;). Persistence of H5 and H7 avian influenza viruses in water. . Avian Dis 51: 285–289. [CrossRef] [PubMed]
    [Google Scholar]
  5. Chen C. J., Chen G. W., Wang C. H., Huang C. H., Wang Y. C., Shih S. R..( 2010;). Differential localization and function of PB1-F2 derived from different strains of influenza A virus. . J Virol 84: 10051–10062. [CrossRef] [PubMed]
    [Google Scholar]
  6. Chen W., Calvo P. A., Malide D., Gibbs J., Schubert U., Bacik I., Basta S., O'Neill R., Schickli J. et al.( 2001;). A novel influenza A virus mitochondrial protein that induces cell death. . Nat Med 7: 1306–1312. [CrossRef] [PubMed]
    [Google Scholar]
  7. Cho J. G., Deen J., Dee S. A..( 2007;). Influence of isolate pathogenicity on the aerosol transmission of Porcine reproductive and respiratory syndrome virus. . Can J Vet Res 71: 23–27.[PubMed]
    [Google Scholar]
  8. Conan A., Goutard F. L., Sorn S., Vong S..( 2012;). Biosecurity measures for backyard poultry in developing countries: a systematic review. . BMC Vet Res 8: 240. [CrossRef] [PubMed]
    [Google Scholar]
  9. Deventhiran J., Kumar S. R. P., Raghunath S., Leroith T., Elankumaran S..( 2015;). PB1-F2 protein does not impact the virulence of triple-reassortant H3N2 swine influenza virus in pigs but alters pathogenicity and transmission in turkeys. . J Virol 90: 222–231. [CrossRef]
    [Google Scholar]
  10. Gibbs J. S., Malide D., Hornung F., Bennink J. R., Yewdell J. W..( 2003;). The influenza A virus PB1-F2 protein targets the inner mitochondrial membrane via a predicted basic amphipathic helix that disrupts mitochondrial function. . J Virol 77: 7214–7224. [CrossRef] [PubMed]
    [Google Scholar]
  11. Hinshaw V. S., Webster R. G., Turner B..( 1979;). Water-bone transmission of influenza A viruses?. Intervirology 11: 66–68. [CrossRef] [PubMed]
    [Google Scholar]
  12. Hoffmann E., Neumann G., Kawaoka Y., Hobom G., Webster R. G..( 2000;). A DNA transfection system for generation of influenza A virus from eight plasmids. . Proc Natl Acad Sci U S A 97: 6108–6113. [CrossRef] [PubMed]
    [Google Scholar]
  13. Hulse-Post D. J., Franks J., Boyd K., Salomon R., Hoffmann E., Yen H. L., Webby R. J., Walker D., Nguyen T. D. et al.( 2007;). Molecular changes in the polymerase genes (PA and PB1) associated with high pathogenicity of H5N1 influenza virus in mallard ducks. . J Virol 81: 8515–8524. [CrossRef] [PubMed]
    [Google Scholar]
  14. Hutchinson E. C., Charles P. D., Hester S. S., Thomas B., Trudgian D., Martínez-Alonso M., Fodor E..( 2015;). Erratum: Conserved and host-specific features of influenza virion architecture. . Nat Commun 6: 6446. [CrossRef] [PubMed]
    [Google Scholar]
  15. Iqbal M., Yaqub T., Mukhtar N., Shabbir M. Z., McCauley J. W..( 2013;). Infectivity and transmissibility of H9N2 avian influenza virus in chickens and wild terrestrial birds. . Vet Res 44: 100. [CrossRef] [PubMed]
    [Google Scholar]
  16. Kamal R. P., Kumar A., Davis C. T., Tzeng W. P., Nguyen T., Donis R. O., Katz J. M., York I. A..( 2015;). Emergence of highly pathogenic avian influenza A(H5N1) virus PB1-F2 variants and their virulence in BALB/c mice. . J Virol 89: 5835–5846. [CrossRef] [PubMed]
    [Google Scholar]
  17. Krumbholz A., Philipps A., Oehring H., Schwarzer K., Eitner A., Wutzler P., Zell R..( 2011;). Current knowledge on PB1-F2 of influenza A viruses. . Med Microbiol Immunol 200: 69–75. [CrossRef] [PubMed]
    [Google Scholar]
  18. Le Goffic R., Bouguyon E., Chevalier C., Vidic J., Da Costa B., Leymarie O., Bourdieu C., Decamps L., Dhorne-Pollet S. et al.( 2010;). Influenza A virus protein PB1-F2 exacerbates IFN-beta expression of human respiratory epithelial cells. . J Immunol 185: 4812–4823. [CrossRef] [PubMed]
    [Google Scholar]
  19. Leymarie O., Embury-Hyatt C., Chevalier C., Jouneau L., Moroldo M., Da Costa B., Berhane Y., Delmas B., Weingartl H. M. et al.( 2014;). PB1-F2 attenuates virulence of highly pathogenic avian H5N1 influenza virus in chickens. . PLoS One 9:,e100679. [CrossRef] [PubMed]
    [Google Scholar]
  20. Long J. S., Giotis E. S., Moncorgé O., Frise R., Mistry B., James J., Morisson M., Iqbal M., Vignal A. et al.( 2016;). Species difference in ANP32A underlies influenza A virus polymerase host restriction. . Nature 529: 101–104. [CrossRef] [PubMed]
    [Google Scholar]
  21. Mazur I., Anhlan D., Mitzner D., Wixler L., Schubert U., Ludwig S..( 2008;). The proapoptotic influenza A virus protein PB1-F2 regulates viral polymerase activity by interaction with the PB1 protein. . Cell Microbiol 10: 1140–1152. [CrossRef] [PubMed]
    [Google Scholar]
  22. McAuley J. L., Hornung F., Boyd K. L., Smith A. M., McKeon R., Bennink J., Yewdell J. W., McCullers J. A..( 2007;). Expression of the 1918 influenza A virus PB1-F2 enhances the pathogenesis of viral and secondary bacterial pneumonia. . Cell Host Microbe 2: 240–249. [CrossRef] [PubMed]
    [Google Scholar]
  23. OFFLU( 2014;). Influenza A Cleavage Sites Version 4. .
  24. Olsen B., Munster V. J., Wallensten A., Waldenström J., Osterhaus A. D., Fouchier R. A..( 2006;). Global patterns of influenza A virus in wild birds. . Science 312: 384–388. [CrossRef] [PubMed]
    [Google Scholar]
  25. Pena L., Vincent A. L., Loving C. L., Henningson J. N., Lager K. M., Lorusso A., Perez D. R..( 2012;). Restored PB1-F2 in the 2009 pandemic H1N1 influenza virus has minimal effects in swine. . J Virol 86: 5523–5532. [CrossRef] [PubMed]
    [Google Scholar]
  26. Penzes Z., Tibbles K., Shaw K., Britton P., Brown T. D., Cavanagh D..( 1994;). Characterization of a replicating and packaged defective RNA of avian coronavirus infectious bronchitis virus. . Virology 203: 286–293. [CrossRef] [PubMed]
    [Google Scholar]
  27. Reperant L. A., Kuiken T., Osterhaus A. D. M. E..( 2012;). Influenza viruses: from birds to humans. . Hum Vaccin Immunother 8: 7–16. [CrossRef]
    [Google Scholar]
  28. Schmolke M., Manicassamy B., Pena L., Sutton T., Hai R., Varga Z. T., Hale B. G., Steel J., Pérez D. R. et al.( 2011;). Differential contribution of PB1-F2 to the virulence of highly pathogenic H5N1 influenza A virus in mammalian and avian species. . PLoS Pathog 7:,e1002186. [CrossRef] [PubMed]
    [Google Scholar]
  29. Shaw M. L., Stone K. L., Colangelo C. M., Gulcicek E. E., Palese P..( 2008;). Cellular proteins in influenza virus particles. . PLoS Pathog 4:,e1000085. [CrossRef] [PubMed]
    [Google Scholar]
  30. Spackman E., Senne D. A., Myers T. J., Bulaga L. L., Garber L. P., Perdue M. L., Lohman K., Daum L. T., Suarez D. L..( 2002;). Development of a real-time reverse transcriptase PCR assay for type A influenza virus and the avian H5 and H7 hemagglutinin subtypes. . J Clin Microbiol 40: 3256–3260. [CrossRef] [PubMed]
    [Google Scholar]
  31. Tamura K., Stecher G., Peterson D., Filipski A., Kumar S..( 2013;). mega6: molecular evolutionary genetics analysis version 6.0. . Mol Biol Evol 30: 2725–2729. [CrossRef] [PubMed]
    [Google Scholar]
  32. To K. K., Ng K. H., Que T. L., Chan J. M., Tsang K. Y., Tsang A. K., Chen H., Yuen K. Y..( 2012;). Avian influenza A H5N1 virus: a continuous threat to humans. . Emerg Microbes Infect 1:,e25. [CrossRef] [PubMed]
    [Google Scholar]
  33. Trifonov V., Racaniello V., Rabadan R..( 2009;). The contribution of the PB1-F2 protein to the fitness of influenza A viruses and its recent evolution in the 2009 influenza A (H1N1) pandemic virus. . PLoS Curr 1: RRN1006. [CrossRef] [PubMed]
    [Google Scholar]
  34. Tufail M., Sajjad M., Zulfiqar M., Sohail S. M., Ahmad I..( 2012;). Economic of backyard poultry in Tehsil Matta district Swat. . Sarhad J. Agric 28: 485–492.
    [Google Scholar]
  35. Webster R. G., Bean W. J., Gorman O. T., Chambers T. M., Kawaoka Y..( 1992;). Evolution and ecology of influenza A viruses. . Microbiol Rev 56: 152–179.[PubMed]
    [Google Scholar]
  36. Westgeest K. B., Russell C. A., Lin X., Spronken M., Bestebroer T. M., Bahl J., van Beek R., Skepner E., Halpin R. A. et al.( 2014;). Genomewide analysis of reassortment and evolution of human influenza A(H3N2) viruses circulating between 1968 and 2011. . J Virol 88: 2844–2857. [CrossRef] [PubMed]
    [Google Scholar]
  37. WHO( 2006;). Collecting, Preserving and Shipping Specimens for the Diagnosis of Avian Influenza A(H5N1) Virus Infection Guide for Field Operations. Edited by Healing T.. Geneva:: World Health Organization;.
    [Google Scholar]
  38. Wise H. M., Barbezange C., Jagger B. W., Dalton R. M., Gog J. R., Curran M. D., Taubenberger J. K., Anderson E. C., Digard P..( 2011;). Overlapping signals for translational regulation and packaging of influenza A virus segment 2. . Nucleic Acids Res 39: 7775–7790.[CrossRef]
    [Google Scholar]
  39. Yamada H., Chounan R., Higashi Y., Kurihara N., Kido H..( 2004;). Mitochondrial targeting sequence of the influenza A virus PB1-F2 protein and its function in mitochondria. . FEBS Lett 578: 331–336. [CrossRef] [PubMed]
    [Google Scholar]
  40. Yu X., Jin T., Cui Y., Pu X., Li J., Xu J., Liu G., Jia H., Liu D. et al.( 2014;). Influenza H7N9 and H9N2 viruses: coexistence in poultry linked to human H7N9 infection and genome characteristics. . J Virol 88: 3423–3431. [CrossRef] [PubMed]
    [Google Scholar]
  41. Zamarin D., Ortigoza M. B., Palese P..( 2006;). Influenza A virus PB1-F2 protein contributes to viral pathogenesis in mice. . J Virol 80: 7976–7983. [CrossRef] [PubMed]
    [Google Scholar]
  42. Zell R., Krumbholz A., Eitner A., Krieg R., Halbhuber K. J., Wutzler P..( 2007;). Prevalence of PB1-F2 of influenza A viruses. . J Gen Virol 88: 536–546. [CrossRef] [PubMed]
    [Google Scholar]
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