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

Abstract

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.

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

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Accessions

GenBank/EMBL/DDBJ

Data deposits

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

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Acknowledgements

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.

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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.

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The authors declare no competing financial interests.

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

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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). https://doi.org/10.1038/nature12515

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