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Several new highly pathogenic (HP) H5 avian influenza virus (AIV) have been detected in poultry farms from south-western France since November 2015, among which an HP H5N1. The zoonotic potential and origin of these AIVs immediately became matters of concern. One virus of each subtype H5N1 (150169a), H5N2 (150233) and H5N9 (150236) was characterised. All proved highly pathogenic for poultry as demonstrated molecularly by the presence of a polybasic cleavage site in their HA protein – with a sequence (HQRRKR/GLF) previously unknown among avian H5 HPAI viruses – or experimentally by the in vivo demonstration of an intravenous pathogenicity index of 2.9 for the H5N1 HP isolate. Phylogenetic analyses based on the full genomes obtained by NGS confirmed that the eight viral segments of the three isolates were all part of avian Eurasian phylogenetic lineage but differed from the Gs/Gd/1/96-like lineage. The study of the genetic characteristics at specific amino acid positions relevant for modulating the adaptation to and the virulence for mammals showed that presently, these viruses possess most molecular features characteristic of AIV and lack some major characteristics required for efficient respiratory transmission to or between humans. The three isolates are therefore predicted to have no significant pandemic potential.


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  1. Haase M, Starick E, Fereidouni S, Strebelow G, Grund C, Seeland A, et al. Possible sources and spreading routes of highly pathogenic avian influenza virus subtype H5N1 infections in poultry and wild birds in Central Europe in 2007 inferred through likelihood analyses. Infect Genet Evol. 2010;10(7):1075-84.  https://doi.org/10.1016/j.meegid.2010.07.005  PMID: 20624487 
  2. Hars J, Ruette S, Benmergui M, Fouque C, Fournier JY, Legouge A, et al. The epidemiology of the highly pathogenic H5N1 avian influenza in Mute Swan (Cygnus olor) and other Anatidae in the Dombes region (France), 2006. J Wildl Dis. 2008;44(4):811-23.  https://doi.org/10.7589/0090-3558-44.4.811  PMID: 18957637 
  3. Gall-Reculé GL, Briand FX, Schmitz A, Guionie O, Massin P, Jestin V. Double introduction of highly pathogenic H5N1 avian influenza virus into France in early 2006. Avian Pathol. 2008;37(1):15-23.  https://doi.org/10.1080/03079450701774835  PMID: 18202945 
  4. Starick E, Beer M, Hoffmann B, Staubach C, Werner O, Globig A, et al. Phylogenetic analyses of highly pathogenic avian influenza virus isolates from Germany in 2006 and 2007 suggest at least three separate introductions of H5N1 virus. Vet Microbiol. 2008;128(3-4):243-52.  https://doi.org/10.1016/j.vetmic.2007.10.012  PMID: 18031958 
  5. European Food Safety Authority (EFSA). Scientific Opinion of the Panel on Animal Health and Welfare on a request from The European Commission on Animal health and welfare aspects of avian influenza and the risk of its introduction into the EU poultry holdings. EFSA J. 2008;715:1-161.
  6. World Organisation for Animal Health (OIE). Rapport de notification immediate. [Immediate notification report]. OIE: Paris; 14 Dec 2016. French. Available from: http://www.oie.int/wahis_2/public%5C.%5Ctemp%5Creports/fr_imm_0000021909_20161215_141530.pdf
  7. Smith GJ, Donis RO,World Health Organization/World Organisation for Animal Health / Food and Agriculture Organization (WHO/OIE/FAO) H5 Evolution Working Group. Nomenclature updates resulting from the evolution of avian influenza A(H5) virus clades, 2.2.1, and 2.3.4 during 2013-2014. Influenza Other Respir Viruses. 2015;9(5):271-6.  https://doi.org/10.1111/irv.12324 
  8. European Food Safety Authority (EFSA). Highly pathogenic avian influenza A subtype H5N8. EFSA J. 2014;12(12):3941.  https://doi.org/10.2903/j.efsa.2014.3941 
  9. Food and Agriculture Organization of the United Nations (FAO). Avian influenza A(H5N6): the latest addition to emerging zoonotic avian influenza threats in East and Southeast Asia. Rome: FAO; Nov 2014. Available from: http://www.fao.org/3/a-i4199e.pdf
  10. World Health Organization (WHO). Updated unified nomenclature system for the highly pathogenic H5N1 avian influenza viruses. Geneva: WHO; Oct 2011. Available from: http://www.who.int/influenza/gisrs_laboratory/h5n1_nomenclature/en/
  11. World Health Organization (WHO). Antigenic and genetic characteristics of zoonotic influenza viruses and development of candidate vaccine for pandemic preparedness. Wkly Epidemiol Rec. 2015;12(90):11.
  12. Agence nationale de sécurité sanitaire de l’alimentation, de l’environnement et du travail (ANSES). Avis de l'Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail relatif au risque Influenza aviaire. [Opinion of the French Agency for Food, Environmental and Occupational Health and Safety regarding avian influenza risk]. Maisons-Alfort: ANSES; 14 Dec 2015. French. Available from: https://www.anses.fr/fr/system/files/SANT2015sa0241.pdf
  13. Briand FX, Le Gall-Reculé G, Guillou-Cloarec C, Ogor K, Jestin V. Phylogeny and genotyping of recent avian low-pathogenic H5 subtype influenza viruses from French ducks. J Gen Virol. 2010;91(Pt 4):960-70.  https://doi.org/10.1099/vir.0.016733-0  PMID: 20016038 
  14. Cherbonnel M, Lamandé J, Allée C, Schmitz A, Ogor K, Le Gall-Reculé G, et al. Virologic findings in selected free-range mule duck farms at high risk for avian influenza infection. Avian Dis. 2007;51(1) Suppl;408-13.  https://doi.org/10.1637/7595-040306R1.1  PMID: 17494595 
  15. World Organisation for Animal Health (OIE). Immediate notification of H5N1 highly pathogenic avian influenza in France. REF OIE 19171, Report Date: 24/11/2015, Country: France. 2015; Report 24 Nov 2015. Available from: http://www.oie.int/wahis_2/public%5C.%5Ctemp%5Creports/fr_imm_0000019171_20151125_164439.pdf
  16. Guerry I, Sadonès H, Schmitz A, Niqueux E, Briand F-X, Jestin V. Bilan de la surveillance de l’influenza aviaire et de la maladie de Newcastle en France en 2013. [Summary of surveillance for avian Influenza and Newcastle disease in France, 2013]. Bull Epid Santé Anim Alim. 2014;64:54-9. Available from: http://bulletinepidemiologique.mag.anses.fr/sites/default/files/BEP-mg-BE64-art14.pdf
  17. Jestin V, Schmitz A, Niqueux E, Briand FX, Brochet AL, Picault JP, et al. Maintien des objectifs et modalités de la surveillance de l’influenza aviaire en 2009: bilan stable par rapport à 2008. [Maintained objectives and means for surveillance of avian influenza in 2009 : Stable situation as compared with 2008]. Bull Epid Santé Anim Alim. 2010;40:41-46. French. Available from: http://bulletinepidemiologique.mag.anses.fr/sites/default/files/BEP-mg-BE40_0.pdf
  18. Sadonès H, Hars J, Schmitz A, Briand FX, Niqueux E. Surveillance de l’influenza aviaire et de la maladie de Newcastle en France en 2011. [Summary of surveillance for avian Influenza and Newcastle disease in France, 2011]. Bull Epid Santé Anim Alim. 2012;54:49-53. French. Available from: http://bulletinepidemiologique.mag.anses.fr/sites/default/files/BEP-mg-BE54.pdf
  19. Sadonès H, Schmitz A, Niqueux N, Briand FX, Jestin V. Surveillance de l’influenza aviaire en France en 2010. [Summary of surveillance for avian Influenza and Newcastle disease in France, 2010]. Bull Epid Santé Anim Alim. 2011;46:44-48. French. Available from: http://bulletinepidemiologique.mag.anses.fr/sites/default/files/BEP-mg-BE46.pdf
  20. Slomka MJ, Coward VJ, Banks J, Löndt BZ, Brown IH, Voermans J, et al. Identification of sensitive and specific avian influenza polymerase chain reaction methods through blind ring trials organized in the European Union. Avian Dis. 2007;51(1) Suppl;227-34.  https://doi.org/10.1637/7674-063006R1.1  PMID: 17494558 
  21. Spackman E, Senne DA, Myers TJ, Bulaga LL, Garber LP, Perdue ML, et al. 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. 2002;40(9):3256-60.  https://doi.org/10.1128/JCM.40.9.3256-3260.2002  PMID: 12202562 
  22. Gall A, Hoffmann B, Harder T, Grund C, Höper D, Beer M. Design and validation of a microarray for detection, hemagglutinin subtyping, and pathotyping of avian influenza viruses. J Clin Microbiol. 2009;47(2):327-34.  https://doi.org/10.1128/JCM.01330-08  PMID: 19052173 
  23. Bao Y, Bolotov P, Dernovoy D, Kiryutin B, Zaslavsky L, Tatusova T, et al. The influenza virus resource at the National Center for Biotechnology Information. J Virol. 2008;82(2):596-601.  https://doi.org/10.1128/JVI.02005-07  PMID: 17942553 
  24. World Organisation for Animal Health (OIE) / Food and Agriculture Organisation (FAO) Network of expertise on animal Influenza (OFFLU). Influenza A cleavage sites 2016. OIE/FAO. Available from: http://www.offlu.net/fileadmin/home/en/resource-centre/pdf/Influenza_A_Cleavage_Sites.pdf
  25. World Organisation for Animal Health (OIE). Chapter 2.3.4, Avian Influenza. in Manual of diagnostic tests and vaccines for terrestrial animals Paris, France: OIE; 2015. http://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/2.03.04_AI.pdf
  26. Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. Mol Biol Evol. 2013;30(12):2725-9.  https://doi.org/10.1093/molbev/mst197  PMID: 24132122 
  27. Centers for Disease Control and Prevention (CDC). H5N1 genetic changes inventory: a tool for influenza surveillance and preparedness. Atlanta: CDC; 21 Jun 2012. Available from: http://www.cdc.gov/flu/pdf/avianflu/h5n1-inventory.pdf
  28. Neumann G, Kawaoka Y. Transmission of influenza A viruses. Virology. 2015;479-480:234-46.  https://doi.org/10.1016/j.virol.2015.03.009  PMID: 25812763 
  29. Puzelli S, Rossini G, Facchini M, Vaccari G, Di Trani L, Di Martino A, et al. . Human infection with highly pathogenic A(H7N7) avian influenza virus, Italy, 2013. Emerg Infect Dis. 2014;20(10):1745-9.  https://doi.org/10.3201/eid2010.140512  PMID: 25271444 
  30. Bodewes R, Bestebroer TM, van der Vries E, Verhagen JH, Herfst S, Koopmans MP, et al. Avian Influenza A(H10N7) virus-associated mass deaths among harbor seals. Emerg Infect Dis. 2015;21(4):720-2.  https://doi.org/10.3201/eid2104.141675  PMID: 25811303 
  31. Hu Y, Liu X, Li S, Guo X, Yang Y, Jin M. Complete genome sequence of a novel H4N1 influenza virus isolated from a pig in central China. J Virol. 2012;86(24):13879.  https://doi.org/10.1128/JVI.02726-12  PMID: 23166273 
  32. Linster M, van Boheemen S, de Graaf M, Schrauwen EJ, Lexmond P, Mänz B, et al. Identification, characterization, and natural selection of mutations driving airborne transmission of A/H5N1 virus. Cell. 2014;157(2):329-39.  https://doi.org/10.1016/j.cell.2014.02.040  PMID: 24725402 
  33. Walther T, Karamanska R, Chan RW, Chan MC, Jia N, Air G, et al. Glycomic analysis of human respiratory tract tissues and correlation with influenza virus infection. PLoS Pathog. 2013;9(3):e1003223.  https://doi.org/10.1371/journal.ppat.1003223  PMID: 23516363 
  34. Imai M, Watanabe T, Hatta M, Das SC, Ozawa M, Shinya K, et al. Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature. 2012;486(7403):420-8. PMID: 22722205 
  35. Herfst S, Imai M, Kawaoka Y, Fouchier RA. Avian influenza virus transmission to mammals. Curr Top Microbiol Immunol. 2014;385:137-55.  https://doi.org/10.1007/82_2014_387  PMID: 25048542 
  36. Rodriguez-Frandsen A, Alfonso R, Nieto A. Influenza virus polymerase: Functions on host range, inhibition of cellular response to infection and pathogenicity. Virus Res. 2015;209:23-38.  https://doi.org/10.1016/j.virusres.2015.03.017  PMID: 25916175 
  37. Influenza Research database (IRD). IRD Search tools. [Accessed Dec 2015]. Available from: http://www.fludb.org/brc/search_landing.spg?decorator=influenza

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