Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

The genesis and source of the H7N9 influenza viruses causing human infections in China


A novel H7N9 influenza A virus first detected in March 2013 has since caused more than 130 human infections in China, resulting in 40 deaths1,2. Preliminary analyses suggest that the virus is a reassortant of H7, N9 and H9N2 avian influenza viruses, and carries some amino acids associated with mammalian receptor binding, raising concerns of a new pandemic1,3,4. However, neither the source populations of the H7N9 outbreak lineage nor the conditions for its genesis are fully known5. Using a combination of active surveillance, screening of virus archives, and evolutionary analyses, here we show that H7 viruses probably transferred from domestic duck to chicken populations in China on at least two independent occasions. We show that the H7 viruses subsequently reassorted with enzootic H9N2 viruses to generate the H7N9 outbreak lineage, and a related previously unrecognized H7N7 lineage. The H7N9 outbreak lineage has spread over a large geographic region and is prevalent in chickens at live poultry markets, which are thought to be the immediate source of human infections. Whether the H7N9 outbreak lineage has, or will, become enzootic in China and neighbouring regions requires further investigation. The discovery here of a related H7N7 influenza virus in chickens that has the ability to infect mammals experimentally, suggests that H7 viruses may pose threats beyond the current outbreak. The continuing prevalence of H7 viruses in poultry could lead to the generation of highly pathogenic variants and further sporadic human infections, with a continued risk of the virus acquiring human-to-human transmissibility.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it


Prices may be subject to local taxes which are calculated during checkout

Figure 1: Phylogenies of haemagglutinin, neuraminidase and PB2 genes.
Figure 2: Evolutionary pathways of the H7N9 and H7N7 viruses.

Accession codes



Data deposits

All sequences generated by this study have been deposited in GenBank under accession numbers KF258943KF260956 and KF297287KF297322 (Supplementary Table 3).


  1. Gao, R. et al. Human infection with a novel avian-origin influenza A (H7N9) virus. N. Engl. J. Med. 368, 1888–1897 (2013)

    Article  CAS  PubMed  Google Scholar 

  2. World Health Organization. Number of confirmed human cases of avian influenza A(H7N9) reported to World Health Organization; (2013)

  3. Liu, D. et al. Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: phylogenetic, structural, and coalescent analyses. Lancet 381, 1926–1932 (2013)

    Article  PubMed  Google Scholar 

  4. Kageyama, T. et al. Genetic analysis of novel avian A(H7N9) influenza viruses isolated from patients in China, February to April 2013. Euro Surveill. 18, 20453 (2013)

    CAS  PubMed  Google Scholar 

  5. Hvistendahl, M., Normile, D. & Cohen, J. Influenza. Despite large research effort, H7N9 continues to baffle. Science 340, 414–415 (2013)

    Article  CAS  ADS  PubMed  Google Scholar 

  6. Guo, Y. J. et al. Characterization of the pathogenicity of members of the newly established H9N2 influenza virus lineages in Asia. Virology 267, 279–288 (2000)

    Article  CAS  PubMed  Google Scholar 

  7. Duan, L. et al. Influenza virus surveillance in migratory ducks and sentinel ducks at Poyang Lake, China. Influenza Other Respi. Viruses 5 (suppl. 1). 65–68 (2011)

    Google Scholar 

  8. Tharakaraman, K. et al. Glycan receptor binding of the influenza A virus H7N9 hemagglutinin. Cell 153, 1486–1493 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Xiong, X. et al. Receptor binding by an H7N9 influenza virus from humans. Nature 499, 496–499 (2013)

    Article  CAS  ADS  PubMed  Google Scholar 

  10. Cheung, C. L. et al. Establishment of influenza A virus (H6N1) in minor poultry species in southern China. J. Virol. 81, 10402–10412 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Yamada, S. et al. Biological and structural characterization of a host-adapting amino acid in influenza virus. PLoS Pathog. 6, e1001034 (2010)

    Article  PubMed  PubMed Central  Google Scholar 

  12. Zhu, H. et al. Infectivity, transmission, and pathology of human-isolated H7N9 influenza virus in ferrets and pigs. Science 341, 183–186 (2013)

    Article  CAS  ADS  PubMed  Google Scholar 

  13. Xu, J., Lu, S., Wang, H. & Chen, C. Reducing exposure to avian influenza H7N9. Lancet 381, 1815–1816 (2013)

    Article  PubMed  Google Scholar 

  14. Shortridge, K. F. et al. Interspecies transmission of influenza viruses: H5N1 virus and a Hong Kong SAR perspective. Vet. Microbiol. 74, 141–147 (2000)

    Article  CAS  PubMed  Google Scholar 

  15. Anisimova, M., Gil, M., Dufayard, J. F., Dessimoz, C. & Gascuel, O. Survey of branch support methods demonstrates accuracy, power, and robustness of fast likelihood-based approximation schemes. Syst. Biol. 60, 685–699 (2011)

    Article  PubMed  PubMed Central  Google Scholar 

  16. Guindon, S. et al. New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Syst. Biol. 59, 307–321 (2010)

    Article  CAS  PubMed  Google Scholar 

  17. Stamatakis, A. RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models. Bioinformatics 22, 2688–2690 (2006)

    Article  CAS  PubMed  Google Scholar 

  18. Drummond, A. J., Suchard, M. A., Xie, D. & Rambaut, A. Bayesian phylogenetics with BEAUti and the BEAST 1.7. Mol. Biol. Evol. 29, 1969–1973 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Murrell, B. et al. Detecting individual sites subject to episodic diversifying selection. PLoS Genet. 8, e1002764 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Pond, S. L., Frost, S. D. & Muse, S. V. HyPhy: hypothesis testing using phylogenies. Bioinformatics 21, 676–679 (2005)

    Article  CAS  PubMed  Google Scholar 

  21. Pupko, T., Pe’er, I., Shamir, R. & Graur, D. A fast algorithm for joint reconstruction of ancestral amino acid sequences. Mol. Biol. Evol. 17, 890–896 (2000)

    Article  CAS  PubMed  Google Scholar 

  22. Huang, K. et al. Establishment and lineage replacement of H6 influenza viruses in domestic ducks in southern China. J. Virol. 86, 6075–6083 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Edgar, R. C. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 32, 1792–1797 (2004)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Drummond, A. J., Ho, S. Y., Phillips, M. J. & Rambaut, A. Relaxed phylogenetics and dating with confidence. PLoS Biol. 4, e88 (2006)

    Article  PubMed  PubMed Central  Google Scholar 

  25. Shapiro, B., Rambaut, A. & Drummond, A. J. Choosing appropriate substitution models for the phylogenetic analysis of protein-coding sequences. Mol. Biol. Evol. 23, 7–9 (2006)

    Article  CAS  PubMed  Google Scholar 

  26. Minin, V. N., Bloomquist, E. W. & Suchard, M. A. Smooth skyride through a rough skyline: Bayesian coalescent-based inference of population dynamics. Mol. Biol. Evol. 25, 1459–1471 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Lam, T. T. et al. Systematic phylogenetic analysis of influenza A virus reveals many novel mosaic genome segments. Infect. Genet. Evol. 18, 367–378 (2013)

    Article  PubMed  Google Scholar 

  28. Delport, W., Poon, A. F., Frost, S. D. & Kosakovsky Pond, S. L. Datamonkey 2010: a suite of phylogenetic analysis tools for evolutionary biology. Bioinformatics 26, 2455–2457 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references


We thank our colleagues from the Joint Influenza Research Centre (SUMC/HKU) and the State Key Laboratory of Emerging Infectious Diseases for their technical assistance. This study was supported by the National Institutes of Health (National Institute of Allergy and Infectious Diseases contract HSN266200700005C), Li Ka Shing Foundation, the Area of Excellence Scheme of the University Grants Committee of the Hong Kong SAR (grant AoE/M-12/06), Shenzhen Peacock Plan High-End Talents Program (KQTD201203), the University Development Fund (HKU) and the Innovation and Technology Commission of the Hong Kong Government. T.T.-Y.L. was supported in part by a Newton International Fellowship of the Royal Society. Metabiota's involvement was supported by the US Agency for International Development (USAID) Emerging Pandemic Threats Program, PREDICT project, under the terms of Cooperative Agreement Number GHN-A-OO-09-00010-00. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under Grant Agreement no. 278433-PREDEMICS, ERC Grant agreement no. 260864 and the Wellcome Trust (grant 092807) to A.R. and S.J.L.

Author information

Authors and Affiliations



Y.G., H.Z. and T.T.-Y.L. conceived the study; J.W., Y. Shen, B.Z., L.D., C.Y.-H.L., W.H., Z.O. and X.C. conducted surveillance; H.Z., J.W., C.-L.C., C.M., L.L., Y.C., L.Z., H.L., Y.L., A.F. and D.J.K. performed virus isolation, sequencing and animal experiments; T.T.-Y.L., A.R., O.G.P., H.Z., D.K.S., S.J.L., L.L.M.P., J.S.M.P., G.M.L., Y. Shu, R.G.W, R.J.W. and Y.G. contributed to the analysis; D.K.S. and T.T.-Y.L. wrote the manuscript; Y.G., H.Z., O.G.P. and A.R. edited the manuscript.

Corresponding authors

Correspondence to Huachen Zhu or Yi Guan.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Figures 1-14, a Supplementary Discussion and Supplementary Tables 1-5. (PDF 5824 kb)

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Lam, TY., Wang, J., Shen, Y. et al. The genesis and source of the H7N9 influenza viruses causing human infections in China. Nature 502, 241–244 (2013).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing