Archives of Virology

, Volume 163, Issue 7, pp 1779–1793 | Cite as

Co-circulation of multiple genotypes of influenza A (H7N9) viruses in eastern China, 2016-2017

  • Xian Qi
  • Xiaofei An
  • Yongjun Jiao
  • Huiyan Yu
  • Ke Xu
  • Lunbiao Cui
  • Shenjiao Wang
  • Fei Deng
  • Xiang Huo
  • Haodi Huang
  • Qigang Dai
  • Changjun Bao
Original Article


Five epidemic waves of human infection with influenza A (H7N9) virus have emerged in China since spring 2013. We previously described the epidemiological characterization of the fifth wave in Jiangsu province. In this study, 41 H7N9 viruses from patients and live-poultry markets were isolated and sequenced to further elucidate the genetic features of viruses of the fifth wave in Jiangsu province. Phylogenetic analysis revealed substantial genetic diversity in the internal genes, and 18 genotypes were identified from the 41 H7N9 virus strains. Furthermore, our data revealed that 41 isolates from Jiangsu contained the G186V and Q226L/I mutations in their haemagglutinin (HA) protein, which may increase the ability of these viruses to bind the human receptor. Four basic amino acid insertions were not observed in the HA cleavage sites of 167 H7N9 viruses from Jiangsu, which revealed that highly pathogenic avian influenza (HPAI) H7N9 viruses did not spread to Jiangsu province in the fifth wave. These findings revealed that multiple genotypes of H7N9 viruses co-circulated in the fifth wave in Jiangsu province, which indicated that the viruses have undergone ongoing evolution with genetic mutation and reassortment. Our study highlights the need to constantly monitor the evolution of H7N9 viruses and reinforce systematic influenza surveillance of humans, birds, and pigs in China.



This study was supported by Jiangsu Provincial Medical Talent Project (No. ZDRCA2016031 and ZDRC A2016032), Science & Technology Demonstration Project for Major Emerging Infectious Diseases Control and Prevention (No. BE2015714, BE2017749), Key Medical Discipline of Epidemiology (No. ZDXK A2016008) and the ‘333’ Project in Jiangsu Province.

Compliance with ethical standards

Conflict of interest

The authors declare that we have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of Jiangsu Provincial Center for Disease Control and Prevention.

Informed consent

Informed consent was obtained from all individual participants included in this study.


  1. 1.
    Belser JA, Bridges CB, Katz JM, Tumpey TM (2009) Past, present, and possible future human infection with influenza virus A subtype H7. Emerg Infect Dis 15(6):859–865CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Chen H, Yuan H, Gao R, Zhang J, Wang D, Xiong Y, Fan G, Yang F, Li X, Zhou J et al (2014) Clinical and epidemiological characteristics of a fatal case of avian influenza A H10N8 virus infection: a descriptive study. Lancet 383(9918):714–721CrossRefPubMedGoogle Scholar
  3. 3.
    Gao R, Cao B, Hu Y, Feng Z, Wang D, Hu W, Chen J, Jie Z, Qiu H, Xu K et al (2013) Human infection with a novel avian-origin influenza A (H7N9) virus. N Engl J Med 368(20):1888–1897CrossRefPubMedGoogle Scholar
  4. 4.
    Pan M, Gao R, Lv Q, Huang S, Zhou Z, Yang L, Li X, Zhao X, Zou X, Tong W et al (2016) Human infection with a novel, highly pathogenic avian influenza A (H5N6) virus: Virological and clinical findings. J Infect 72(1):52–59CrossRefPubMedGoogle Scholar
  5. 5.
    Peiris JS, de Jong MD, Guan Y (2007) Avian influenza virus (H5N1): a threat to human health. Clin Microbiol Rev 20(2):243–267CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Wei SH, Yang JR, Wu HS, Chang MC, Lin JS, Lin CY, Liu YL, Lo YC, Yang CH, Chuang JH et al (2013) Human infection with avian influenza A H6N1 virus: an epidemiological analysis. Lancet Respir Med 1(10):771–778CrossRefPubMedGoogle Scholar
  7. 7.
    Lam TT, Wang J, Shen Y, Zhou B, Duan L, Cheung CL, Ma C, Lycett SJ, Leung CY, Chen X et al (2013) The genesis and source of the H7N9 influenza viruses causing human infections in China. Nature 502(7470):241–244CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Zhou L, Tan Y, Kang M, Liu F, Ren R, Wang Y, Chen T, Yang Y, Li C, Wu J et al (2017) Preliminary epidemiology of human infections with highly pathogenic avian influenza A(H7N9) virus, China, 2017. Emerg Infect Dis 23(8):1355–1359CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Kile JC, Ren R, Liu L, Greene CM, Roguski K, Iuliano AD, Jang Y, Jones J, Thor S, Song Y et al (2017) Update: increase in human infections with novel asian lineage avian influenza A(H7N9) viruses during the fifth epidemic - China, October 1, 2016-August 7, 2017. MMWR Morb Mortal Wkly Rep 66(35):928–932CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Wang X, Jiang H, Wu P, Uyeki TM, Feng L, Lai S, Wang L, Huo X, Xu K, Chen E et al (2017) Epidemiology of avian influenza A H7N9 virus in human beings across five epidemics in mainland China, 2013-17: an epidemiological study of laboratory-confirmed case series. Lancet Infect Dis 17(8):822–832CrossRefPubMedGoogle Scholar
  11. 11.
    Huo X, Chen L, Qi X, Huang H, Dai Q, Yu H, Xia Y, Liu W, Xu K, Ma W et al (2017) Significantly elevated number of human infections with H7N9 virus in Jiangsu in eastern China, October 2016 to January 2017. Euro Surveill 22(13):30496CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Hoffmann E, Stech J, Guan Y, Webster RG, Perez DR (2001) Universal primer set for the full-length amplification of all influenza A viruses. Adv Virol 146(12):2275–2289Google Scholar
  13. 13.
    Drummond AJ, Rambaut A (2007) BEAST: Bayesian evolutionary analysis by sampling trees. BMC Evol Biol 7:214CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Wang D, Yang L, Zhu W, Zhang Y, Zou S, Bo H, Gao R, Dong J, Huang W, Guo J et al (2016) Two outbreak sources of influenza A (H7N9) viruses have been established in China. J Virol 90(12):5561–5573CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Shi Y, Zhang W, Wang F, Qi J, Wu Y, Song H, Gao F, Bi Y, Zhang Y, Fan Z et al (2013) Structures and receptor binding of hemagglutinins from human-infecting H7N9 influenza viruses. Science 342(6155):243–247CrossRefPubMedGoogle Scholar
  16. 16.
    Xu R, de Vries RP, Zhu X, Nycholat CM, McBride R, Yu W, Paulson JC, Wilson IA (2013) Preferential recognition of avian-like receptors in human influenza A H7N9 viruses. Science 342(6163):1230–1235CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Zhu W, Zhou J, Li Z, Yang L, Li X, Huang W, Zou S, Chen W, Wei H, Tang J et al (2017) Biological characterisation of the emerged highly pathogenic avian influenza (HPAI) A(H7N9) viruses in humans, in mainland China, 2016 to 2017. Euro Surveill 22(19):30533CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    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 U S A 102(51):18590–18595CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Mok CK, Lee HH, Lestra M, Nicholls JM, Chan MC, Sia SF, Zhu H, Poon LL, Guan Y, Peiris JS (2014) Amino acid substitutions in polymerase basic protein 2 gene contribute to the pathogenicity of the novel A/H7N9 influenza virus in mammalian hosts. J Virol 88(6):3568–3576CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Marjuki H, Mishin VP, Chesnokov AP, De La Cruz JA, Davis CT, Villanueva JM, Fry AM, Gubareva LV (2015) Neuraminidase mutations conferring resistance to oseltamivir in influenza A(H7N9) viruses. J Virol 89(10):5419–5426CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Marjuki H, Mishin VP, Chesnokov AP, Jones J, De La Cruz JA, Sleeman K, Tamura D, Nguyen HT, Wu HS, Chang FY et al (2015) Characterization of drug-resistant influenza A(H7N9) variants isolated from an oseltamivir-treated patient in Taiwan. J Infect Dis 211(2):249–257CrossRefPubMedGoogle Scholar
  22. 22.
    Yang L, Zhu W, Li X, Chen M, Wu J, Yu P, Qi S, Huang Y, Shi W, Dong J et al (2017) Genesis and spread of newly emerged highly pathogenic H7N9 avian viruses in mainland China. J Virol 91:e01277PubMedPubMedCentralGoogle Scholar
  23. 23.
    Chen H, Smith GJ, Li KS, Wang J, Fan XH, Rayner JM, Vijaykrishna D, Zhang JX, Zhang LJ, Guo CT et al (2006) Establishment of multiple sublineages of H5N1 influenza virus in Asia: implications for pandemic control. Proc Natl Acad Sci USA 103(8):2845–2850CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Huang K, Zhu H, Fan X, Wang J, Cheung CL, Duan L, Hong W, Liu Y, Li L, Smith DK et al (2012) Establishment and lineage replacement of H6 influenza viruses in domestic ducks in southern China. J Virol 86(11):6075–6083CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Ma C, Lam TT, Chai Y, Wang J, Fan X, Hong W, Zhang Y, Li L, Liu Y, Smith DK et al (2015) Emergence and evolution of H10 subtype influenza viruses in poultry in China. J Virol 89(7):3534–3541CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Pu J, Wang S, Yin Y, Zhang G, Carter RA, Wang J, Xu G, Sun H, Wang M, Wen C et al (2015) Evolution of the H9N2 influenza genotype that facilitated the genesis of the novel H7N9 virus. Proc Natl Acad Sci USA 112(2):548–553CrossRefPubMedGoogle Scholar
  27. 27.
    Jin Y, Ren H, Teng Y, Hu M, Peng X, Yue J, Liang L (2017) Novel reassortment of avian influenza A(H7N9) virus with subtype H6N6 and H5N6 viruses circulating in Guangdong Province China. J Infect 75(2):179–182CrossRefPubMedGoogle Scholar
  28. 28.
    Qi X, Qian YH, Bao CJ, Guo XL, Cui LB, Tang FY, Ji H, Huang Y, Cai PQ, Lu B et al (2013) Probable person to person transmission of novel avian influenza A (H7N9) virus in Eastern China, 2013: epidemiological investigation. BMJ 347:f4752CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Zhu Y, Qi X, Cui L, Zhou M, Wang H (2013) Human co-infection with novel avian influenza A H7N9 and influenza A H3N2 viruses in Jiangsu province, China. Lancet 381(9883):2134CrossRefPubMedGoogle Scholar

Copyright information

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

Authors and Affiliations

  • Xian Qi
    • 1
  • Xiaofei An
    • 2
  • Yongjun Jiao
    • 1
  • Huiyan Yu
    • 1
  • Ke Xu
    • 1
  • Lunbiao Cui
    • 1
  • Shenjiao Wang
    • 1
  • Fei Deng
    • 1
  • Xiang Huo
    • 1
  • Haodi Huang
    • 1
  • Qigang Dai
    • 1
  • Changjun Bao
    • 1
  1. 1.Jiangsu Provincial Center for Disease Control and PreventionJiangsuChina
  2. 2.Department of Endocrinology, Jiangsu Province Hospital of Chinese MedicineAffiliated Hospital of Nanjing University of Chinese MedicineNanjingChina

Personalised recommendations