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Abstract

Since 2013 the occurrence of human infections by a novel avian H7N9 influenza virus in China has demonstrated the continuing threat posed by zoonotic pathogens1,2. Although the first outbreak wave that was centred on eastern China was seemingly averted, human infections recurred in October 2013 (refs 3, 4, 5, 6, 7). It is unclear how the H7N9 virus re-emerged and how it will develop further; potentially it may become a long-term threat to public health. Here we show that H7N9 viruses have spread from eastern to southern China and become persistent in chickens, which has led to the establishment of multiple regionally distinct lineages with different reassortant genotypes. Repeated introductions of viruses from Zhejiang to other provinces and the presence of H7N9 viruses at live poultry markets have fuelled the recurrence of human infections. This rapid expansion of the geographical distribution and genetic diversity of the H7N9 viruses poses a direct challenge to current disease control systems. Our results also suggest that H7N9 viruses have become enzootic in China and may spread beyond the region, following the pattern previously observed with H5N1 and H9N2 influenza viruses8,9.

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Accessions

Primary accessions

GenBank/EMBL/DDBJ

Data deposits

All sequences generated by this study have been deposited in GenBank/EMBL/DDBJ under accession numbers KP413163KP418563. Detailed phylogenetic inferences are available from http://dx.doi.org/10.5061/dryad.5q7kf.

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Acknowledgements

We thank C. L. Cheung, H. Y. Liang and G. C. Yu for their assistance in data processing; Z. H. Ou, Z. Y. Jin, T. Y. Leung, K. K. Chan, Y. R. Qiu, J. Z. Xie, N. Qi, J. Zhou, P. Y. Huang and all staff members at the Joint Influenza Research Centre (SUMC/HKU) for technical support, the four collaborative hospitals in Shenzhen for human sample collection, and P. Lemey for his advice on phylogeographic analysis. This study was supported by the Shenzhen Peacock Plan High-End Talents Program (KQTD201203), the Health and Medical Research Fund of the Hong Kong Government (RRG-10 and RRG-14), the University Grants Committee of Hong Kong (Area of Excellence Scheme grant AoE/M-12/06), the National Institute of Allergy and Infectious Diseases (contract HHSN272201400006C), and the Li Ka Shing Foundation. E.C.H. is supported by an NHMRC Australia Fellowship (AF30).

Author information

Author notes

    • Tommy Tsan-Yuk Lam
    • , Boping Zhou
    • , Jia Wang
    • , Yujuan Chai
    • , Yongyi Shen
    •  & Xinchun Chen

    These authors contributed equally to this work.

Affiliations

  1. State Key Laboratory of Emerging Infectious Diseases (HKU-Shenzhen Branch), Shenzhen Third People’s Hospital, Shenzhen 518112, China

    • Tommy Tsan-Yuk Lam
    • , Boping Zhou
    • , Xinchun Chen
    • , Lian Duan
    • , Peiwen Chen
    • , Junfei Jiang
    • , Leo Lit Man Poon
    • , Joseph S. M. Peiris
    • , Yi Guan
    •  & Huachen Zhu
  2. Joint Influenza Research Centre (SUMC/HKU), Shantou University Medical College (SUMC), Shantou 515041, China

    • Tommy Tsan-Yuk Lam
    • , Jia Wang
    • , Yujuan Chai
    • , Yongyi Shen
    • , Chi Ma
    • , Wenshan Hong
    • , Lian Duan
    • , Peiwen Chen
    • , Yu Zhang
    • , Lifeng Li
    • , David K. Smith
    • , Yi Guan
    •  & Huachen Zhu
  3. Centre of Influenza Research, School of Public Health, The University of Hong Kong (HKU), Hong Kong, China

    • Tommy Tsan-Yuk Lam
    • , Jia Wang
    • , Yujuan Chai
    • , Yongyi Shen
    • , Chi Ma
    • , Lian Duan
    • , Junfei Jiang
    • , Yu Zhang
    • , Lifeng Li
    • , Leo Lit Man Poon
    • , David K. Smith
    • , Gabriel M. Leung
    • , Joseph S. M. Peiris
    • , Yi Guan
    •  & Huachen Zhu
  4. Key Laboratory of Emergency Detection for Public Health of Zhejiang Province, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang 310051, China

    • Yin Chen
    •  & Yanjun Zhang
  5. Division of Virology, Department of Infectious Diseases, St Jude Children’s Research Hospital, Memphis, Tennessee 38105, USA

    • Richard J. Webby
  6. Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Biological Sciences and Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia

    • Edward C. Holmes

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Contributions

Y.G., H.Z. and T.T.-Y.L. conceived the study; B.Z., J.W., Y.S., X.C., W.H., L.D., P.C., J.J. conducted surveillance; Y.C., C.M., Yu Z., L.L. performed sequencing; H.Z, T.T.-Y.L., E.C.H., D.K.S., Y.G. performed the analysis and wrote the manuscript; Y.C., Ya.Z., L.L.M.P., R.J.W., G.M.L., J.S.M.P. participated in the discussion and interpretation of findings. T.T.-Y.L., B.Z., J.W., Y.C., Y.S., X.C. contributed equally to this work.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Yi Guan or Huachen Zhu.

Extended data

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains a Supplementary Discussion with additional references and Supplementary Data (see separate excel file for data in table format).

Excel files

  1. 1.

    Supplementary Data

    This file shows the haemagglutinin inhibition (HI) assays of H7N9 viruses in table format.

About this article

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DOI

https://doi.org/10.1038/nature14348

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