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Characterization of an H5N8 influenza A virus isolated from chickens during an outbreak of severe avian influenza in Japan in April 2014

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Abstract

A highly pathogenic avian influenza virus (HPAIV) of subtype H5N8, A/chicken/Kumamoto/1-7/2014, was isolated from a Japanese chicken farm during an outbreak in April 2014. Phylogenetic analysis revealed that this virus belonged to HA clade 2.3.4.4. All eight genomic segments showed high sequence similarity to those of the H5N8 subtype HPAIVs A/broiler duck/Korea/Buan2/2014 and A/baikal teal/Korea/Donglim3/2014, which were isolated in Korea in January 2014. Intranasal experimental infection of chickens and ducks with A/chicken/Kumamoto/1-7/2014 was performed to assess the pathogenicity of the virus in chickens and the potential for waterfowl to act as a virus reservoir and carrier. A high-titer virus challenge (106 EID50 per animal) was lethal in chickens, but they were unaffected by lower virus doses (102 EID50 or 104 EID50 per animal). Virus challenge at all doses examined was found to result in asymptomatic infection of ducks. An HI assay revealed that A/chicken/Kumamoto/1-7/2014 possessed relatively low cross-reactivity with H5 viruses belonging to clades other than clade 2.3.4.4. These results suggest that waterfowl may be able to spread the virus even if they possess antibodies resulting from a previous infection with H5 HPAIV that was antigenically distinguishable from viruses belonging to clade 2.3.4.4.

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References

  1. Bridges CB, Lim W, Hu-Primmer J, Sims L, Fukuda K, Mak KH, Rowe T, Thompson WW, Conn L, Lu X, Cox NJ, Katz JM (2002) Risk of influenza A (H5N1) infection among poultry workers, Hong Kong, 1997–1998. J Infect Dis 185(8):1005–1010. doi:10.1086/340044

    Article  PubMed  Google Scholar 

  2. de Vries RP, Zhu X, McBride R, Rigter A, Hanson A, Zhong G, Hatta M, Xu R, Yu W, Kawaoka Y, de Haan CA, Wilson IA, Paulson JC (2014) Hemagglutinin receptor specificity and structural analyses of respiratory droplet-transmissible H5N1 viruses. J Virol 88(1):768–773. doi:10.1128/JVI.02690-13

    Article  PubMed Central  PubMed  Google Scholar 

  3. Fan S, Deng G, Song J, Tian G, Suo Y, Jiang Y, Guan Y, Bu Z, Kawaoka Y, Chen H (2009) Two amino acid residues in the matrix protein M1 contribute to the virulence difference of H5N1 avian influenza viruses in mice. Virology 384(1):28–32. doi:10.1016/j.virol.2008.11.044

    Article  CAS  PubMed  Google Scholar 

  4. Gu M, Zhao G, Zhao K, Zhong L, Huang J, Wan H, Wang X, Liu W, Liu H, Peng D, Liu X (2013) Novel variants of clade 2.3.4 highly pathogenic avian influenza A(H5N1) viruses, China. Emerg Infect Dis 19(12):2021–2024. doi:10.3201/eid1912.130340

    Article  PubMed Central  PubMed  Google Scholar 

  5. Hatta M, Gao P, Halfmann P, Kawaoka Y (2001) Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science 293(5536):1840–1842. doi:10.1126/science.1062882

    Article  CAS  PubMed  Google Scholar 

  6. Imai M, Watanabe T, Hatta M, Das SC, Ozawa M, Shinya K, Zhong G, Hanson A, Katsura H, Watanabe S, Li C, Kawakami E, Yamada S, Kiso M, Suzuki Y, Maher EA, Neumann G, Kawaoka Y (2012) Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature 486(7403):420–428. doi:10.1038/nature10831

    CAS  PubMed Central  PubMed  Google Scholar 

  7. Jiao P, Tian G, Li Y, Deng G, Jiang Y, Liu C, Liu W, Bu Z, Kawaoka Y, Chen H (2008) A single-amino-acid substitution in the NS1 protein changes the pathogenicity of H5N1 avian influenza viruses in mice. J Virol 82(3):1146–1154. doi:10.1128/JVI.01698-07

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Kanehira K, Takemae N, Uchida Y, Hikono H, Saito T (2014) Reassortant swine influenza viruses isolated in Japan contain genes from pandemic A(H1N1) 2009. Microbiol Immunol 58(6):327–341. doi:10.1111/1348-0421.12152

    Article  CAS  PubMed  Google Scholar 

  9. Kida H, Yanagawa R, Matsuoka Y (1980) Duck influenza lacking evidence of disease signs and immune response. Infect Immun 30(2):547–553

    CAS  PubMed Central  PubMed  Google Scholar 

  10. Kilpatrick AM, Chmura AA, Gibbons DW, Fleischer RC, Marra PP, Daszak P (2006) Predicting the global spread of H5N1 avian influenza. Proc Natl Acad Sci USA 103(51):19368–19373. doi:10.1073/pnas.0609227103

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Kim Y-I, Pascua PNQ, Kwon H-I, Lim G-J, Kim E-H, Yoon S-W, Park S-J, Kim SM, Choi E-J, Si Y-J, Lee O-J, Shim W-S, Kim S-W, Mo I-P, Bae Y, Lim YT, Sung MH, Kim C-J, Webby RJ, Webster RG, Choi YK (2014) Pathobiological features of a novel, highly pathogenic avian influenza A(H5N8) virus. Emerg Microbes Infect 3:e75. doi:10.1038/emi.2014.75

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Lee YJ, Kang HM, Lee EK, Song BM, Jeong J, Kwon YK, Kim HR, Lee KJ, Hong MS, Jang I, Choi KS, Kim JY, Lee HJ, Kang MS, Jeong OM, Baek JH, Joo YS, Park YH (2014) Lee HS (2014) Novel reassortant influenza A(H5N8) viruses, South Korea. Emerg Infect Dis 20(6):1087–1089. doi:10.3201/eid2006.140233

    Article  PubMed Central  PubMed  Google Scholar 

  13. Li Q, Wang X, Gu M, Zhu J, Hao X, Gao Z, Sun Z, Hu J, Hu S, Wang X, Liu X, Liu X (2014) Novel H5 clade 2.3.4.6 viruses with both alpha-2,3 and alpha-2,6 receptor binding properties may pose a pandemic threat. Vet Res 45:127. doi:10.1186/s13567-014-0127-2

    Article  PubMed Central  PubMed  Google Scholar 

  14. Linster M, van Boheemen S, de Graaf M, Schrauwen EJ, Lexmond P, Manz B, Bestebroer TM, Baumann J, van Riel D, Rimmelzwaan GF, Osterhaus AD, Matrosovich M, Fouchier RA, Herfst S (2014) Identification, characterization, and natural selection of mutations driving airborne transmission of A/H5N1 virus. Cell 157(2):329–339. doi:10.1016/j.cell.2014.02.04

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Liu Q, Qiao C, Marjuki H, Bawa B, Ma J, Guillossou S, Webby RJ, Richt JA, Ma W (2012) Combination of PB2 271A and SR polymorphism at positions 590/591 is critical for viral replication and virulence of swine influenza virus in cultured cells and in vivo. J Virol 86(2):1233–1237. doi:10.1128/JVI.05699-11

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Mase M, Tsukamoto K, Imada T, Imai K, Tanimura N, Nakamura K, Yamamoto Y, Hitomi T, Kira T, Nakai T, Kiso M, Horimoto T, Kawaoka Y, Yamaguchi S (2005) Characterization of H5N1 influenza A viruses isolated during the 2003–2004 influenza outbreaks in Japan. Virology 332(1):167–176. doi:10.1016/j.virol.2004.11.016

    Article  CAS  PubMed  Google Scholar 

  17. Nakamura K, Imada T, Imai K, Yamamoto Y, Tanimura N, Yamada M, Mase M, Tsukamoto K, Yamaguchi S (2008) Pathology of specific-pathogen-free chickens inoculated with H5N1 avian influenza viruses isolated in Japan in 2004. Avian Dis 52(1):8–13

    Article  PubMed  Google Scholar 

  18. Nidom CA, Takano R, Yamada S, Sakai-Tagawa Y, Daulay S, Aswadi D, Suzuki T, Suzuki Y, Shinya K, Iwatsuki-Horimoto K, Muramoto Y, Kawaoka Y (2010) Influenza A (H5N1) viruses from pigs, Indonesia. Emerg Infect Dis 16(10):1515–1523. doi:10.3201/eid1610.100508

    Article  PubMed Central  PubMed  Google Scholar 

  19. Pinto LH, Holsinger LJ, Lamb RA (1992) Influenza virus M2 protein has ion channel activity. Cell 69(3):517–528

    Article  CAS  PubMed  Google Scholar 

  20. Ramey AM, Spackman E, Yeh JY, Fujita G, Konishi K, Uchida K, Reed JA, Wilcox BR, Brown JD, Stallknecht DE (2013) Antibodies to H5 subtype avian influenza virus and Japanese encephalitis virus in northern pintails (Anas acuta) sampled in Japan. Jpn J Vet Res 61:117–123

    PubMed  Google Scholar 

  21. Reed LJ, Muench HA (1938) A simple method for estimating fifty percent endpoints. Am J Hyg 27(3):493–497

    Google Scholar 

  22. Sakoda Y, Ito H, Uchida Y, Okamatsu M, Yamamoto N, Soda K, Nomura N, Kuribayashi S, Shichinohe S, Sunden Y, Umemura T, Usui T, Ozaki H, Yamaguchi T, Murase T, Ito T, Saito T, Takada A, Kida H (2012) Reintroduction of H5N1 highly pathogenic avian influenza virus by migratory water birds, causing poultry outbreaks in the 2010–2011 winter season in Japan. J Gen Virol 93(3):541–550. doi:10.1099/vir.0.037572-0

    Article  CAS  PubMed  Google Scholar 

  23. Samson M, Pizzorno A, Abed Y, Boivin G (2013) Influenza virus resistance to neuraminidase inhibitors. Antiviral Res 98(2):174–185. doi:10.1016/j.antiviral.2013.03.014

    Article  CAS  PubMed  Google Scholar 

  24. Schmolke M, Manicassamy B, Pena L, Sutton T, Hai R, Varga ZT, Hale BG, Steel J, Perez DR, Garcia-Sastre A (2011) Differential contribution of PB1-F2 to the virulence of highly pathogenic H5N1 influenza A virus in mammalian and avian species. PLoS Pathog 7(8):e1002186. doi:10.1371/journal.ppat.1002186

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Srinivasan K, Raman R, Jayaraman A, Viswanathan K, Sasisekharan R (2013) Quantitative description of glycan-receptor binding of influenza A virus H7 hemagglutinin. PloS One 8(2):e49597. doi:10.1371/journal.pone.0049597

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Steel J, Lowen AC, Mubareka S, Palese P (2009) Transmission of influenza virus in a mammalian host is increased by PB2 amino acids 627K or 627E/701N. PLoS Pathog 5(1):e1000252. doi:10.1371/journal.ppat.1000252

    Article  PubMed Central  PubMed  Google Scholar 

  27. Uchida Y, Chaichoune K, Wiriyarat W, Watanabe C, Hayashi T, Patchimasiri T, Nuansrichay B, Parchariyanon S, Okamatsu M, Tsukamoto K, Takemae N, Ratanakorn P, Yamaguchi S, Saito T (2008) Molecular epidemiological analysis of highly pathogenic avian influenza H5N1 subtype isolated from poultry and wild bird in Thailand. Virus Res 138(1–2):70–80. doi:10.1016/j.virusres.2008.08.007

    Article  CAS  PubMed  Google Scholar 

  28. Uchida Y, Suzuki Y, Shirakura M, Kawaguchi A, Nobusawa E, Tanikawa T, Hikono H, Takemae N, Mase M, Kanehira K, Hayashi T, Tagawa Y, Tashiro M, Saito T (2012) Genetics and infectivity of H5N1 highly pathogenic avian influenza viruses isolated from chickens and wild birds in Japan during 2010-11. Virus Res 170(1–2):109–117. doi:10.1016/j.virusres.2012.09.004

    Article  CAS  PubMed  Google Scholar 

  29. Watanabe Y, Ibrahim MS, Ellakany HF, Kawashita N, Mizuike R, Hiramatsu H, Sriwilaijaroen N, Takagi T, Suzuki Y, Ikuta K (2011) Acquisition of human-type receptor binding specificity by new H5N1 influenza virus sublineages during their emergence in birds in Egypt. PLoS Pathog 7(5):e1002068. doi:10.1371/journal.ppat.1002068

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. World Health Organization/World Organisation for Animal, Health Food Agriculture Organization, H. N. Evolution Working Group (2014) Revised and updated nomenclature for highly pathogenic avian influenza A (H5N1) viruses. Influenza Other Respir Viruses 8(3):384–388. doi:10.1111/irv.12230

    Article  Google Scholar 

  31. World Health Organization/World Organisation for Animal, Health Food Agriculture Organization, H. N. Evolution Working Group (2015) WHO/OIE/FAO H5 Working Group reports a new clade designated 2.3.4.4. Promed Archive Number: 20150114.3090250

  32. World Health Organization (2014). http://www.who.int/influenza/human_animal_interface/en/. Accessed 13 April 2015

  33. World Organisation for Animal Health (2014) Chapter 2.3.4 Avian influenza. Manual of diagnostic tests and vaccines for terrestrial animals 2014. http://www.oie.int/international-standard-setting/terrestrial-manual/access-online/. Accessed 13 April 2015

  34. World Organisation for Animal Health (2014) Update on highly pathogenic avian influenza in animals (type H5 and H7). http://www.oie.int/en/animal-health-in-the-world/update-on-avian-influenza/2014/. Accessed 13 April 2015

  35. World Organisation for Animal Health (2015) Update on highly pathogenic avian influenza in animals (type H5 and H7). http://www.oie.int/en/animal-health-in-the-world/update-on-avian-influenza/2015/. Accessed 13 April 2015

  36. Wu H, Peng X, Xu L, Jin C, Cheng L, Lu X, Xie T, Yao H, Wu N (2014) Novel reassortant influenza A(H5N8) viruses in domestic ducks, Eastern China. Emerg Infect Dis 20(8):1315–1318. doi:10.3201/eid2008.140339

    Article  PubMed Central  PubMed  Google Scholar 

  37. Xu X, Subbarao Cox NJ, Guo Y (1999) Genetic characterization of the pathogenic influenza A/Goose/Guangdong/1/96 (H5N1) virus: similarity of its hemagglutinin gene to those of H5N1 viruses from the 1997 outbreaks in Hong Kong. Virology 261(1):15–19

    Article  CAS  PubMed  Google Scholar 

  38. Yamada S, Suzuki Y, Suzuki T, Le MQ, Nidom CA, Sakai-Tagawa Y, Muramoto Y, Ito M, Kiso M, Horimoto T, Shinya K, Sawada T, Kiso M, Usui T, Murata T, Lin Y, Hay A, Haire LF, Stevens DJ, Russell RJ, Gamblin SJ, Skehel JJ, Kawaoka Y (2006) Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors. Nature 444(7117):378–382. doi:10.1038/nature05264

    Article  CAS  PubMed  Google Scholar 

  39. Yamamoto Y, Nakamura K, Yamada M, Mase M (2010) Comparative pathology of chickens and domestic ducks experimentally infected with highly pathogenic avian influenza viruses (H5N1) isolated in Japan in 2007 and 2008. Jpn Agric Res Q 44(1):73–80

    Article  Google Scholar 

  40. Yang H, Chen LM, Carney PJ, Donis RO, Stevens J (2010) Structures of receptor complexes of a North American H7N2 influenza hemagglutinin with a loop deletion in the receptor binding site. PLoS Pathog 6(9):e1001081. doi:10.1371/journal.ppat.1001081

    Article  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

We would like to thank Dr. Masaomi Mori, Kumamoto Prefectural Livestock Hygiene Center, Japan, and Dr. Youn-Jeong Lee of the Animal and Plant Quarantine Agency, Korea, for kindly providing us with viral samples. We would also like to thank Dr. Eri Nobusawa, National Institute of Infectious Diseases, Japan, for providing Anh05 antigen, and post-infection ferret serum against Anh05 and Kum14. This study was partially supported by a research project for improving food safety and animal health from the Ministry of Agriculture, Forestry and Fisheries of Japan.

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Correspondence to Takehiko Saito.

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Kanehira, K., Uchida, Y., Takemae, N. et al. Characterization of an H5N8 influenza A virus isolated from chickens during an outbreak of severe avian influenza in Japan in April 2014. Arch Virol 160, 1629–1643 (2015). https://doi.org/10.1007/s00705-015-2428-9

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