Archives of Virology

, Volume 163, Issue 5, pp 1153–1162 | Cite as

Virological and pathological characterization of an avian H1N1 influenza A virus

  • Bon-Sang Koo
  • Hye Kwon Kim
  • Daesub Song
  • Woonsung Na
  • Min-Suk Song
  • Jin Jung Kwon
  • Sook-San Wong
  • Ji Yeong Noh
  • Min-Ju Ahn
  • Doo-Jin Kim
  • Richard J Webby
  • Sun-Woo Yoon
  • Dae Gwin Jeong
Original Article


Gene segments from avian H1N1 influenza A viruses have reassorted with other influenza viruses to generate pandemic strains over the past century. Nevertheless, little effort has been invested in understanding the characteristics of avian H1N1 influenza viruses. Here, we present the genome sequence and a molecular and virological characterization of an avian influenza A virus, A/wild bird/Korea/SK14/2014 (A/SK14, H1N1), isolated from migratory birds in South Korea during the winter season of 2014-2015. Full-genome sequencing and phylogenetic analysis revealed that the virus belongs to the Eurasian avian lineage. Although it retained avian-receptor binding preference, A/SK14 virus also exhibited detectable human-like receptor binding and was able to replicate in differentiated primary normal human bronchial epithelial cells. In animal models, A/SK14 virus was moderately pathogenic in mice, and virus was detected in nasal washes from inoculated guinea pigs, but not in direct-contact guinea pigs. Although A/SK14 showed moderate pathogenicity and no evidence of transmission in a mammalian model, our results suggest that the dual receptor specificity of A/SK14-like virus might allow for a more rapid adaptation to mammals, emphasizing the importance of further continuous surveillance and risk-assessment activities.



We thank Hyun-Woo Lee and Hai Yen Le for technical assistance.


This work was supported by grants from the KRIBB Initiative program, supported by the BioNano Health-Guard Research Center, funded by the Ministry of Science, ICT and Future Planning (MSIP) of Korea as Global Frontier Project (Grant no. H-GUARD 2013M3A6B2078954) and supported by Animal Disease Management Technology Development, Ministry of Agriculture, Food and Rural Affairs (Grant no. 316042-03), and supported by Korea Ministry of Environment (MOE) as “Public Technology Program based on Environmental Policy (no. 2016000210002)”.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

All animal experiments were conducted at the Korea Research Institute of Bioscience and Biotechnology (KRIBB, Daejeon, Korea) and Chungbuk National University (Cheongju, Korea) and were approved by and conducted in accordance with the guidelines of the Institutional Animal Care and Use Committee of KRIBB and Chungbuk National University.

Supplementary material

705_2018_3730_MOESM1_ESM.docx (1.2 mb)
Supplementary material 1 (DOCX 1186 kb)


  1. 1.
    Baek YH, Song MS, Lee EY, Kim YI, Kim EH, Park SJ, Park KJ, Kwon HI, Pascua PN, Lim GJ, Kim S, Yoon SW, Kim MH, Webby RJ, Choi YK (2015) Profiling and characterization of influenza virus N1 strains potentially resistant to multiple neuraminidase inhibitors. J Virol 89:287–299CrossRefPubMedGoogle Scholar
  2. 2.
    Bedford T, Riley S, Barr IG, Broor S, Chadha M, Cox NJ, Daniels RS, Gunasekaran CP, Hurt AC, Kelso A, Klimov A, Lewis NS, Li X, McCauley JW, Odagiri T, Potdar V, Rambaut A, Shu Y, Skepner E, Smith DJ, Suchard MA, Tashiro M, Wang D, Xu X, Lemey P, Russell CA (2015) Global circulation patterns of seasonal influenza viruses vary with antigenic drift. Nature 523:217–220CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Chan RW, Yuen KM, Yu WC, Ho CC, Nicholls JM, Peiris JS, Chan MC (2010) Influenza H5N1 and H1N1 virus replication and innate immune responses in bronchial epithelial cells are influenced by the state of differentiation. PLoS One 5:e8713CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Edgar RC (2004) MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucl Acids Res 32:1792–1797CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Gabriel G, Dauber B, Wolff T, Planz O, Klenk HD, Stech J (2005) The viral polymerase mediates adaptation of an avian influenza virus to a mammalian host. Proc Natl Acad Sci USA 102:18590–18595CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Global Consortium for HN, Related Influenza V (2016) Role for migratory wild birds in the global spread of avian influenza H5N8. Science 354:213–217CrossRefGoogle Scholar
  7. 7.
    Hai R, Schmolke M, Varga ZT, Manicassamy B, Wang TT, Belser JA, Pearce MB, Garcia-Sastre A, Tumpey TM, Palese P (2010) PB1-F2 expression by the 2009 pandemic H1N1 influenza virus has minimal impact on virulence in animal models. J Virol 84:4442–4450CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    He CQ, Ding NZ, Mou X, Xie ZX, Si HL, Qiu R, Ni S, Zhao H, Lu Y, Yan HY, Gao YX, Chen LL, Shen XH, Cao RN (2012) Identification of three H1N1 influenza virus groups with natural recombinant genes circulating from 1918 to 2009. Virology 427:60–66CrossRefPubMedGoogle Scholar
  9. 9.
    Hoffmann E, Stech J, Guan Y, Webster RG, Perez DR (2001) Universal primer set for the full-length amplification of all influenza A viruses. Arch Virol 146:2275–2289CrossRefPubMedGoogle Scholar
  10. 10.
    Kang HM, Lee EK, Song BM, Jeong J, Kim HR, Choi EJ, Shin YK, Lee HS, Lee YJ (2014) Genetic and pathogenic characteristics of H1 avian and swine influenza A viruses. J Gen Virol 95:2118–2126CrossRefPubMedGoogle Scholar
  11. 11.
    Kang HM, Park HY, Lee KJ, Choi JG, Lee EK, Song BM, Lee HS, Lee YJ (2014) Characterization of H7 influenza A virus in wild and domestic birds in Korea. PLoS One 9:e91887CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Kim YI, Pascua PN, Kwon HI, Lim GJ, Kim EH, Yoon SW, Park SJ, Kim SM, Choi EJ, Si YJ, Lee OJ, Shim WS, Kim SW, Mo IP, Bae Y, Lim YT, Sung MH, Kim CJ, Webby RJ, Webster RG, Choi YK (2014) Pathobiological features of a novel, highly pathogenic avian influenza A(H5N8) virus. Emerg Microbes Infect 3:e75CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Kocer ZA, Krauss S, Stallknecht DE, Rehg JE, Webster RG (2012) The potential of avian H1N1 influenza A viruses to replicate and cause disease in mammalian models. PLoS One 7:e41609CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Kocer ZA, Carter R, Wu G, Zhang J, Webster RG (2015) The genomic contributions of Avian H1N1 influenza A viruses to the evolution of mammalian strains. PLoS One 10:e0133795CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Kocer ZA, Krauss S, Zanin M, Danner A, Gulati S, Jones JC, Friedman K, Graham A, Forrest H, Seiler J, Air GM, Webster RG (2015) Possible basis for the emergence of H1N1 viruses with pandemic potential from avian hosts. Emerg Microbes Infect 4:e40CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Koo BS, Kim HK, Na W, Song D, Kim DJ, Yoon SW, Jeong DG (2017) Complete genome sequence of an Avian H1N1 influenza virus strain isolated from migratory birds in the Republic of Korea. Genome Announc 5:e00356-17CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Liu H, Golebiewski L, Dow EC, Krug RM, Javier RT, Rice AP (2010) The ESEV PDZ-binding motif of the avian influenza A virus NS1 protein protects infected cells from apoptosis by directly targeting scribble. J Virol 84:11164–11174CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Lowen AC, Mubareka S, Tumpey TM, Garcia-Sastre A, Palese P (2006) The guinea pig as a transmission model for human influenza viruses. Proc Natl Acad Sci USA 103:9988–9992CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Matrosovich MN, Gambaryan AS (2012) Solid-phase assays of receptor-binding specificity. Methods Mol Biol 865:71–94CrossRefPubMedGoogle Scholar
  20. 20.
    Na W, Lyoo KS, Yoon SW, Yeom M, Kang B, Moon H, Kim HK, Jeong DG, Kim JK, Song D (2016) Attenuation of the virulence of a recombinant influenza virus expressing the naturally truncated NS gene from an H3N8 equine influenza virus in mice. Vet Res 47:115CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Nakajima K, Desselberger U, Palese P (1978) Recent human influenza A (H1N1) viruses are closely related genetically to strains isolated in 1950. Nature 274:334–339CrossRefPubMedGoogle Scholar
  22. 22.
    Nam JH, Shim SM, Song EJ, Espano E, Jeong DG, Song D, Kim JK (2017) Rapid virulence shift of an H5N2 avian influenza virus during a single passage in mice. Arch Virol 162:3017–3024CrossRefPubMedGoogle Scholar
  23. 23.
    Novel Swine-Origin Influenza AVIT, Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S, Garten RJ, Gubareva LV, Xu X, Bridges CB, Uyeki TM (2009) Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 360:2605–2615CrossRefGoogle Scholar
  24. 24.
    Qi L, Kash JC, Dugan VG, Wang R, Jin G, Cunningham RE, Taubenberger JK (2009) Role of sialic acid binding specificity of the 1918 influenza virus hemagglutinin protein in virulence and pathogenesis for mice. J Virol 83:3754–3761CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Reed LJ, Muench H (1938) A simple method of estimating fifty percent endpoints. Am J Hyg 27:493–497Google Scholar
  26. 26.
    Reid AH, Fanning TG, Hultin JV, Taubenberger JK (1999) Origin and evolution of the 1918 “Spanish” influenza virus hemagglutinin gene. Proc Natl Acad Sci USA 96:1651–1656CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Schrauwen EJ, Fouchier RA (2014) Host adaptation and transmission of influenza A viruses in mammals. Emerg Microbes Infect 3:e9CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Si YJ, Lee IW, Kim EH, Kim YI, Kwon HI, Park SJ, Nguyen HD, Kim SM, Kwon JJ, Choi WS, Beak YH, Song MS, Kim CJ, Webby RJ, Choi YK (2017) Genetic characterisation of novel, highly pathogenic avian influenza (HPAI) H5N6 viruses isolated in birds, South Korea, November 2016. Euro Surveill 22(1):30434Google Scholar
  29. 29.
    Smith GJ, Vijaykrishna D, Bahl J, Lycett SJ, Worobey M, Pybus OG, Ma SK, Cheung CL, Raghwani J, Bhatt S, Peiris JS, Guan Y, Rambaut A (2009) Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic. Nature 459:1122–1125CrossRefPubMedGoogle Scholar
  30. 30.
    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:e1000252CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Subbarao K, Klimov A, Katz J, Regnery H, Lim W, Hall H, Perdue M, Swayne D, Bender C, Huang J, Hemphill M, Rowe T, Shaw M, Xu X, Fukuda K, Cox N (1998) Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness. Science 279:393–396CrossRefPubMedGoogle Scholar
  32. 32.
    Yoon SW, Webby RJ, Webster RG (2014) Evolution and ecology of influenza A viruses. Curr Top Microbiol Immunol 385:359–375PubMedGoogle Scholar
  33. 33.
    Yoon SW, Chen N, Ducatez MF, McBride R, Barman S, Fabrizio TP, Webster RG, Haliloglu T, Paulson JC, Russell CJ, Hertz T, Ben-Tal N, Webby RJ (2015) Changes to the dynamic nature of hemagglutinin and the emergence of the 2009 pandemic H1N1 influenza virus. Sci Rep 5:12828CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Zhang Y, Zhang Q, Gao Y, He X, Kong H, Jiang Y, Guan Y, Xia X, Shu Y, Kawaoka Y, Bu Z, Chen H (2012) Key molecular factors in hemagglutinin and PB2 contribute to efficient transmission of the 2009 H1N1 pandemic influenza virus. J Virol 86:9666–9674CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  • Bon-Sang Koo
    • 1
  • Hye Kwon Kim
    • 1
  • Daesub Song
    • 2
  • Woonsung Na
    • 2
  • Min-Suk Song
    • 3
  • Jin Jung Kwon
    • 3
  • Sook-San Wong
    • 4
  • Ji Yeong Noh
    • 1
  • Min-Ju Ahn
    • 1
    • 5
  • Doo-Jin Kim
    • 1
  • Richard J Webby
    • 4
  • Sun-Woo Yoon
    • 1
    • 5
  • Dae Gwin Jeong
    • 1
    • 5
  1. 1.Infectious Disease Research Center, Korea Research Institute of Bioscience and BiotechnologyDaejeonSouth Korea
  2. 2.Department of Pharmacy, College of PharmacyKorea UniversitySejongSouth Korea
  3. 3.College of Medicine and Medical Research InstituteChungbuk National UniversityChongjuSouth Korea
  4. 4.Department of Infectious DiseasesSt. Jude Children’s Research HospitalMemphisUSA
  5. 5.University of Science and Technology (UST)DaejeonSouth Korea

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