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. 2021 Apr 16;15(4):507–527. doi: 10.1007/s11684-020-0814-5

Avian influenza A (H7N9) virus: from low pathogenic to highly pathogenic

William J Liu 1,2,✉, Haixia Xiao 3, Lianpan Dai 4, Di Liu 5,6,7,8, Jianjun Chen 5,6,7,8, Xiaopeng Qi 9, Yuhai Bi 1,4,7,8, Yi Shi 1,4,7,8, George F Gao 2,4,9, Yingxia Liu 1,✉
PMCID: PMC8190734  PMID: 33860875

Abstract

The avian influenza A (H7N9) virus is a zoonotic virus that is closely associated with live poultry markets. It has caused infections in humans in China since 2013. Five waves of the H7N9 influenza epidemic occurred in China between March 2013 and September 2017. H7N9 with low-pathogenicity dominated in the first four waves, whereas highly pathogenic H7N9 influenza emerged in poultry and spread to humans during the fifth wave, causing wide concern. Specialists and officials from China and other countries responded quickly, controlled the epidemic well thus far, and characterized the virus by using new technologies and surveillance tools that were made possible by their preparedness efforts. Here, we review the characteristics of the H7N9 viruses that were identified while controlling the spread of the disease. It was summarized and discussed from the perspectives of molecular epidemiology, clinical features, virulence and pathogenesis, receptor binding, T-cell responses, monoclonal antibody development, vaccine development, and disease burden. These data provide tools for minimizing the future threat of H7N9 and other emerging and re-emerging viruses, such as SARS-CoV-2.

Keywords: H7N9, HPAIV, epidemiology, clinical features, pathogenesis, hemagglutinin, immunity, vaccine

Acknowledgements

We would like to thank Drs. Decheng Wang, Bilin Liang from CAS Key Laboratory of Special Pathogens and Biosafety, Chinese Academy of Sciences, and Dr. Ying Xu from Nanjing Agricultural University for their assistance during the preparation of this review. This study was supported by the Shenzhen Science and Technology Research and Development Project (No. JCYJ201604271519- 20801), Innovation Unit for Emerging and Re-emerging Virus Adaptive Evolution Study and the Applications in Disease Control (No. 2019-I2M-5-009) and National Mega-projects for Infectious Diseases (No. 2020ZX10001016-005-001). W.J.L. is supported by the Excellent Young Scientist Program of the NSFC (No. 81822040) and Beijing New-star Plan of Science and Technology (No. Z181100006218080). H.X. is supported by Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project (No. TSBICIP-KJGG-004-04). G.F.G. is a leading principal investigator of the National Natural Science Foundation of China Innovative Research Group (No. 81621091).

Footnotes

Compliance with ethical guidelines

William J. Liu, Haixia Xiao, Lianpan Dai, Di Liu, Jianjun Chen, Xiaopeng Qi, Yuhai Bi, Yi Shi, George F. Gao, and Yingxia Liu declare that they have no conflict of interest. This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

Contributor Information

William J. Liu, Email: liujun@ivdc.chinacdc.cn

Yingxia Liu, Email: yingxialiu@hotmail.com.

References

  • 1.Koopmans M, Wilbrink B, Conyn M, Natrop G, van der Nat H, Vennema H, Meijer A, van Steenbergen J, Fouchier R, Osterhaus A, Bosman A. Transmission of H7N7 avian influenza A virus to human beings during a large outbreak in commercial poultry farms in the Netherlands. Lancet. 2004;363(9409):587–593. doi: 10.1016/S0140-6736(04)15589-X. [DOI] [PubMed] [Google Scholar]
  • 2.Gao R, Cao B, Hu Y, Feng Z, Wang D, Hu W, Chen J, Jie Z, Qiu H, Xu K, Xu X, Lu H, Zhu W, Gao Z, Xiang N, Shen Y, He Z, Gu Y, Zhang Z, Yang Y, Zhao X, Zhou L, Li X, Zou S, Zhang Y, Li X, Yang L, Guo J, Dong J, Li Q, Dong L, Zhu Y, Bai T, Wang S, Hao P, Yang W, Zhang Y, Han J, Yu H, Li D, Gao GF, Wu G, Wang Y, Yuan Z, Shu Y. Human infection with a novel avian-origin influenza A (H7N9) virus. N Engl J Med. 2013;368(20):1888–1897. doi: 10.1056/NEJMoa1304459. [DOI] [PubMed] [Google Scholar]
  • 3.Liu D, Shi W, Shi Y, Wang D, Xiao H, Li W, Bi Y, Wu Y, Li X, Yan J, Liu W, Zhao G, Yang W, Wang Y, Ma J, Shu Y, Lei F, Gao GF. Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: phylogenetic, structural, and coalescent analyses. Lancet. 2013;381(9881):1926–1932. doi: 10.1016/S0140-6736(13)60938-1. [DOI] [PubMed] [Google Scholar]
  • 4.Liu J, Xiao H, Wu Y, Liu D, Qi X, Shi Y, Gao GF. H7N9: a low pathogenic avian influenza A virus infecting humans. Curr Opin Virol. 2014;5:91–97. doi: 10.1016/j.coviro.2014.03.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Kile JC, Ren R, Liu L, Greene CM, Roguski K, Iuliano AD, Jang Y, Jones J, Thor S, Song Y, Zhou S, Trock SC, Dugan V, Wentworth DE, Levine MZ, Uyeki TM, Katz JM, Jernigan DB, Olsen SJ, Fry AM, Azziz-Baumgartner E, Davis CT. 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. 2017;66(35):928–932. doi: 10.15585/mmwr.mm6635a2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Zhang F, Bi Y, Wang J, Wong G, Shi W, Hu F, Yang Y, Yang L, Deng X, Jiang S, He X, Liu Y, Yin C, Zhong N, Gao GF. Human infections with recently-emerging highly pathogenic H7N9 avian influenza virus in China. J Infect. 2017;75(1):71–75. doi: 10.1016/j.jinf.2017.04.001. [DOI] [PubMed] [Google Scholar]
  • 7.Quan C, Shi W, Yang Y, Yang Y, Liu X, Xu W, Li H, Li J, Wang Q, Tong Z, Wong G, Zhang C, Ma S, Ma Z, Fu G, Zhang Z, Huang Y, Song H, Yang L, Liu WJ, Liu Y, Liu W, Gao GF, Bi Y. New threats from H7N9 influenza virus: spread and evolution of high-and low-pathogenicity variants with high genomic diversity in wave five. J Virol. 2018;92(11):e00301–18. doi: 10.1128/JVI.00301-18. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Qi W, Jia W, Liu D, Li J, Bi Y, Xie S, Li B, Hu T, Du Y, Xing L, Zhang J, Zhang F, Wei X, Eden JS, Li H, Tian H, Li W, Su G, Lao G, Xu C, Xu B, Liu W, Zhang G, Ren T, Holmes EC, Cui J, Shi W, Gao GF, Liao M. Emergence and adaptation of a novel highly pathogenic H7N9 influenza virus in birds and humans from a 2013 human-infecting low-pathogenic ancestor. J Virol. 2018;92(2):e00921–17. doi: 10.1128/JVI.00921-17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Wang X, Jiang H, Wu P, Uyeki TM, Feng L, Lai S, Wang L, Huo X, Xu K, Chen E, Wang X, He J, Kang M, Zhang R, Zhang J, Wu J, Hu S, Zhang H, Liu X, Fu W, Ou J, Wu S, Qin Y, Zhang Z, Shi Y, Zhang J, Artois J, Fang VJ, Zhu H, Guan Y, Gilbert M, Horby PW, Leung GM, Gao GF, Cowling BJ, Yu H. Epidemiology of avian influenza A H7N9 virus in human beings across five epidemics in mainland of China, 2013–17: an epidemiological study of laboratory-confirmed case series. Lancet Infect Dis. 2017;17(8):822–832. doi: 10.1016/S1473-3099(17)30323-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Kang M, Lau EHY, Guan W, Yang Y, Song T, Cowling BJ, Wu J, Peiris M, He J, Mok CKP. Epidemiology of human infections with highly pathogenic avian influenza A (H7N9) virus in Guangdong, 2016 to 2017. Euro Surveill. 2017;22(27):30568. doi: 10.2807/1560-7917.ES.2017.22.27.30568. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Li H, Cao B. Pandemic and avian influenza A viruses in humans: epidemiology, virology, clinical characteristics, and treatment strategy. Clin Chest Med. 2017;38(1):59–70. doi: 10.1016/j.ccm.2016.11.005. [DOI] [PubMed] [Google Scholar]
  • 12.Han M, Gu J, Gao GF, Liu WJ. China in action: national strategies to combat against emerging infectious diseases. Sci China Life Sci. 2017;60(12):1383–1385. doi: 10.1007/s11427-017-9141-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Wu P, Jiang H, Wu JT, Chen E, He J, Zhou H, Wei L, Yang J, Yang B, Qin Y, Fang VJ, Li M, Tsang TK, Zheng J, Lau EH, Cao Y, Chai C, Zhong H, Li Z, Leung GM, Feng L, Gao GF, Cowling BJ, Yu H. Poultry market closures and human infection with influenza A (H7N9) virus, China, 2013–14. Emerg Infect Dis. 2014;20(11):1891–1894. doi: 10.3201/eid2011.140556. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Yu H, Wu JT, Cowling BJ, Liao Q, Fang VJ, Zhou S, Wu P, Zhou H, Lau EH, Guo D, Ni MY, Peng Z, Feng L, Jiang H, Luo H, Li Q, Feng Z, Wang Y, Yang W, Leung GM. Effect of closure of live poultry markets on poultry-to-person transmission of avian influenza A H7N9 virus: an ecological study. Lancet. 2014;383(9916):541–548. doi: 10.1016/S0140-6736(13)61904-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Gao GF. Influenza and the live poultry trade. Science. 2014;344(6181):235. doi: 10.1126/science.1254664. [DOI] [PubMed] [Google Scholar]
  • 16.Zeng X, Tian G, Shi J, Deng G, Li C, Chen H. Vaccination of poultry successfully eliminated human infection with H7N9 virus in China. Sci China Life Sci. 2018;61(12):1465–1473. doi: 10.1007/s11427-018-9420-1. [DOI] [PubMed] [Google Scholar]
  • 17.Liu WJ, Liu D. The triphibious warfare against viruses. Sci China Life Sci. 2017;60(12):1295–1298. doi: 10.1007/s11427-017-9252-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Gao R, Cao B, Hu Y, Feng Z, Wang D, Hu W, Chen J, Jie Z, Qiu H, Xu K, Xu X, Lu H, Zhu W, Gao Z, Xiang N, Shen Y, He Z, Gu Y, Zhang Z, Yang Y, Zhao X, Zhou L, Li X, Zou S, Zhang Y, Li X, Yang L, Guo J, Dong J, Li Q, Dong L, Zhu Y, Bai T, Wang S, Hao P, Yang W, Zhang Y, Han J, Yu H, Li D, Gao GF, Wu G, Wang Y, Yuan Z, Shu Y. Human infection with a novel avian-origin influenza A (H7N9) virus. N Engl J Med. 2013;368(20):1888–1897. doi: 10.1056/NEJMoa1304459. [DOI] [PubMed] [Google Scholar]
  • 19.Cui L, Liu D, Shi W, Pan J, Qi X, Li X, Guo X, Zhou M, Li W, Li J, Haywood J, Xiao H, Yu X, Pu X, Wu Y, Yu H, Zhao K, Zhu Y, Wu B, Jin T, Shi Z, Tang F, Zhu F, Sun Q, Wu L, Yang R, Yan J, Lei F, Zhu B, Liu W, Ma J, Wang H, Gao GF. Dynamic reassortments and genetic heterogeneity of the human-infecting influenza A (H7N9) virus. Nat Commun. 2014;5(1):3142. doi: 10.1038/ncomms4142. [DOI] [PubMed] [Google Scholar]
  • 20.Lam TT, Wang J, Shen Y, Zhou B, Duan L, Cheung CL, Ma C, Lycett SJ, Leung CY, Chen X, Li L, Hong W, Chai Y, Zhou L, Liang H, Ou Z, Liu Y, Farooqui A, Kelvin DJ, Poon LL, Smith DK, Pybus OG, Leung GM, Shu Y, Webster RG, Webby RJ, Peiris JS, Rambaut A, Zhu H, Guan Y. The genesis and source of the H7N9 influenza viruses causing human infections in China. Nature. 2013;502(7470):241–244. doi: 10.1038/nature12515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Wu A, Su C, Wang D, Peng Y, Liu M, Hua S, Li T, Gao GF, Tang H, Chen J, Liu X, Shu Y, Peng D, Jiang T. Sequential reassortments underlie diverse influenza H7N9 genotypes in China. Cell Host Microbe. 2013;14(4):446–452. doi: 10.1016/j.chom.2013.09.001. [DOI] [PubMed] [Google Scholar]
  • 22.Pu J, Wang S, Yin Y, Zhang G, Carter RA, Wang J, Xu G, Sun H, Wang M, Wen C, Wei Y, Wang D, Zhu B, Lemmon G, Jiao Y, Duan S, Wang Q, Du Q, Sun M, Bao J, Sun Y, Zhao J, Zhang H, Wu G, Liu J, Webster RG. Evolution of the H9N2 influenza genotype that facilitated the genesis of the novel H7N9 virus. Proc Natl Acad Sci USA. 2015;112(2):548–553. doi: 10.1073/pnas.1422456112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Li G, Fox J, 3rd, Liu Z, Liu J, Gao GF, Jin Y, Gao H, Wu M. Lyn mitigates mouse airway remodeling by downregulating the TGF-β3 isoform in house dust mite models. J Immunol. 2013;191(11):5359–5370. doi: 10.4049/jimmunol.1301596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Lam TT, Zhou B, Wang J, Chai Y, Shen Y, Chen X, Ma C, Hong W, Chen Y, Zhang Y, Duan L, Chen P, Jiang J, Zhang Y, Li L, Poon LL, Webby RJ, Smith DK, Leung GM, Peiris JS, Holmes EC, Guan Y, Zhu H. Dissemination, divergence and establishment of H7N9 influenza viruses in China. Nature. 2015;522(7554):102–105. doi: 10.1038/nature14348. [DOI] [PubMed] [Google Scholar]
  • 25.Bi Y, Chen Q, Wang Q, Chen J, Jin T, Wong G, Quan C, Liu J, Wu J, Yin R, Zhao L, Li M, Ding Z, Zou R, Xu W, Li H, Wang H, Tian K, Fu G, Huang Y, Shestopalov A, Li S, Xu B, Yu H, Luo T, Lu L, Xu X, Luo Y, Liu Y, Shi W, Liu D, Gao GF. Genesis, evolution and prevalence of H5N6 avian influenza viruses in China. Cell Host Microbe. 2016;20(6):810–821. doi: 10.1016/j.chom.2016.10.022. [DOI] [PubMed] [Google Scholar]
  • 26.Zhou L, Ren R, Yang L, Bao C, Wu J, Wang D, Li C, Xiang N, Wang Y, Li D, Sui H, Shu Y, Feng Z, Li Q, Ni D. Sudden increase in human infection with avian influenza A (H7N9) virus in China, September — December 2016. Western Pac Surveill Response J. 2017;8(1):6–14. doi: 10.5365/wpsar.2017.8.1.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Su S, Gu M, Liu D, Cui J, Gao GF, Zhou J, Liu X. Epidemiology, evolution, and pathogenesis of H7N9 influenza viruses in five epidemic waves since 2013 in China. Trends Microbiol. 2017;25(9):713–728. doi: 10.1016/j.tim.2017.06.008. [DOI] [PubMed] [Google Scholar]
  • 28.Zhu H, Lam TT, Smith DK, Guan Y. Emergence and development of H7N9 influenza viruses in China. Curr Opin Virol. 2016;16:106–113. doi: 10.1016/j.coviro.2016.01.020. [DOI] [PubMed] [Google Scholar]
  • 29.Chen E, Chen Y, Fu L, Chen Z, Gong Z, Mao H, Wang D, Ni MY, Wu P, Yu Z, He T, Li Z, Gao J, Liu S, Shu Y, Cowling BJ, Xia S, Yu H. Human infection with avian influenza A (H7N9) virus re-emerges in China in winter 2013. Euro Surveill. 2013;18(43):20616. doi: 10.2807/1560-7917.ES2013.18.43.20616. [DOI] [PubMed] [Google Scholar]
  • 30.Xiang D, Pu Z, Luo T, Guo F, Li X, Shen X, Irwin DM, Murphy RW, Liao M, Shen Y. Evolutionary dynamics of avian influenza A H7N9 virus across five waves in mainland China, 2013–2017. J Infect. 2018;77(3):205–211. doi: 10.1016/j.jinf.2018.05.006. [DOI] [PubMed] [Google Scholar]
  • 31.Zhou L, Tan Y, Kang M, Liu F, Ren R, Wang Y, Chen T, Yang Y, Li C, Wu J, Zhang H, Li D, Greene CM, Zhou S, Iuliano AD, Havers F, Ni D, Wang D, Feng Z, Uyeki TM, Li Q. Preliminary epidemiology of human infections with highly pathogenic avian influenza A (H7N9) virus, China, 2017. Emerg Infect Dis. 2017;23(8):1355–1359. doi: 10.3201/eid2308.170640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Wang D, Yang L, Gao R, Zhang X, Tan Y, Wu A, Zhu W, Zhou J, Zou S, Li X, Sun Y, Zhang Y, Liu Y, Liu T, Xiong Y, Xu J, Chen L, Weng Y, Qi X, Guo J, Li X, Dong J, Huang W, Zhang Y, Dong L, Zhao X, Liu L, Lu J, Lan Y, Wei H, Xin L, Chen Y, Xu C, Chen T, Zhu Y, Jiang T, Feng Z, Yang W, Wang Y, Zhu H, Guan Y, Gao GF, Li D, Han J, Wang S, Wu G, Shu Y. Genetic tuning of the novel avian influenza A (H7N9) virus during interspecies transmission, China, 2013. Euro Surveill. 2014;19(25):20836. doi: 10.2807/1560-7917.ES2014.19.25.20836. [DOI] [PubMed] [Google Scholar]
  • 33.Bi Y, Xie Q, Zhang S, Li Y, Xiao H, Jin T, Zheng W, Li J, Jia X, Sun L, Liu J, Qin C, Gao GF, Liu W. Assessment of the internal genes of influenza A (H7N9) virus contributing to high pathogenicity in mice. J Virol. 2015;89(1):2–13. doi: 10.1128/JVI.02390-14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Jin Y, Ren H, Teng Y, Hu M, Peng X, Yue J, Liang L. Novel reassortment of avian influenza A (H7N9) virus with subtype H6N6 and H5N6 viruses circulating in Guangdong Province, China. J Infect. 2017;75(2):179–182. doi: 10.1016/j.jinf.2017.05.006. [DOI] [PubMed] [Google Scholar]
  • 35.To KK, Ng KH, Que TL, Chan JM, Tsang KY, Tsang AK, Chen H, Yuen KY. Avian influenza A H5N1 virus: a continuous threat to humans. Emerg Microbes Infect. 2012;1(9):e25. doi: 10.1038/emi.2012.24. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Gao HN, Lu HZ, Cao B, Du B, Shang H, Gan JH, Lu SH, Yang YD, Fang Q, Shen YZ, Xi XM, Gu Q, Zhou XM, Qu HP, Yan Z, Li FM, Zhao W, Gao ZC, Wang GF, Ruan LX, Wang WH, Ye J, Cao HF, Li XW, Zhang WH, Fang XC, He J, Liang WF, Xie J, Zeng M, Wu XZ, Li J, Xia Q, Jin ZC, Chen Q, Tang C, Zhang ZY, Hou BM, Feng ZX, Sheng JF, Zhong NS, Li LJ. Clinical findings in 111 cases of influenza A (H7N9) virus infection. N Engl J Med. 2013;368(24):2277–2285. doi: 10.1056/NEJMoa1305584. [DOI] [PubMed] [Google Scholar]
  • 37.Yang Y, Wong G, Yang L, Tan S, Li J, Bai B, Xu Z, Li H, Xu W, Zhao X, Quan C, Zheng H, Liu WJ, Liu W, Liu L, Liu Y, Bi Y, Gao GF. Comparison between human infections caused by highly and low pathogenic H7N9 avian influenza viruses in Wave Five: clinical and virological findings. J Infect. 2019;78(3):241–248. doi: 10.1016/j.jinf.2019.01.005. [DOI] [PubMed] [Google Scholar]
  • 38.Wang Q, Zhang Z, Shi Y, Jiang Y. Emerging H7N9 influenza A (novel reassortant avian-origin) pneumonia: radiologic findings. Radiology. 2013;268(3):882–889. doi: 10.1148/radiol.13130988. [DOI] [PubMed] [Google Scholar]
  • 39.Shi J, Xie J, He Z, Hu Y, He Y, Huang Q, Leng B, He W, Sheng Y, Li F, Song Y, Bai C, Gu Y, Jie Z. A detailed epidemiological and clinical description of 6 human cases of avian-origin influenza A (H7N9) virus infection in Shanghai. PLoS One. 2013;8(10):e77651. doi: 10.1371/journal.pone.0077651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Li Q, Zhou L, Zhou M, Chen Z, Li F, Wu H, Xiang N, Chen E, Tang F, Wang D, Meng L, Hong Z, Tu W, Cao Y, Li L, Ding F, Liu B, Wang M, Xie R, Gao R, Li X, Bai T, Zou S, He J, Hu J, Xu Y, Chai C, Wang S, Gao Y, Jin L, Zhang Y, Luo H, Yu H, He J, Li Q, Wang X, Gao L, Pang X, Liu G, Yan Y, Yuan H, Shu Y, Yang W, Wang Y, Wu F, Uyeki TM, Feng Z. Epidemiology of human infections with avian influenza A (H7N9) virus in China. N Engl J Med. 2014;370(6):520–532. doi: 10.1056/NEJMoa1304617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Xu L, Bao L, Deng W, Dong L, Zhu H, Chen T, Lv Q, Li F, Yuan J, Xiang Z, Gao K, Xu Y, Huang L, Li Y, Liu J, Yao Y, Yu P, Li X, Huang W, Zhao X, Lan Y, Guo J, Yong W, Wei Q, Chen H, Zhang L, Qin C. Novel avian-origin human influenza A (H7N9) can be transmitted between ferrets via respiratory droplets. J Infect Dis. 2014;209(4):551–556. doi: 10.1093/infdis/jit474. [DOI] [PubMed] [Google Scholar]
  • 42.Liu WJ, Zou R, Hu Y, Zhao M, Quan C, Tan S, Luo K, Yuan J, Zheng H, Liu J, Liu M, Bi Y, Yan J, Zhu B, Wang D, Wu G, Liu L, Yuen KY, Gao GF, Liu Y. Clinical, immunological and bacteriological characteristics of H7N9 patients nosocomially co-infected by Acinetobacter baumannii: a case control study. BMC Infect Dis. 2018;18(1):664. doi: 10.1186/s12879-018-3447-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Yu L, Wang Z, Chen Y, Ding W, Jia H, Chan JF, To KK, Chen H, Yang Y, Liang W, Zheng S, Yao H, Yang S, Cao H, Dai X, Zhao H, Li J, Bao Q, Chen P, Hou X, Li L, Yuen KY. Clinical, virological, and histopathological manifestations of fatal human infections by avian influenza A (H7N9) virus. Clin Infect Dis. 2013;57(10):1449–1457. doi: 10.1093/cid/cit541. [DOI] [PubMed] [Google Scholar]
  • 44.Yang L, Zhu W, Li X, Chen M, Wu J, Yu P, Qi S, Huang Y, Shi W, Dong J, Zhao X, Huang W, Li Z, Zeng X, Bo H, Chen T, Chen W, Liu J, Zhang Y, Liang Z, Shi W, Shu Y, Wang D. Genesis and spread of newly emerged highly pathogenic H7N9 avian viruses in mainland of China. J Virol. 2017;91(23):e01277–17. doi: 10.1128/JVI.01277-17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.WHO. Monthly Risk Assessment Summary. https://www.who.int/influenza/human_animal_interface/HAI_Risk_Assessment/en/2019. Updated October 23, 2020 (accessed November 15, 2020)
  • 46.Yang Y, Shen C, Li J, Zou R, Wong G, Peng L, Yang L, Fang S, Li J, Li X, Wu W, Jiang X, Zeng L, Lan J, Bi Y, Gao GF, Yuan J, Liu Y. Clinical and virological characteristics of human infections with H7N9 avian influenza virus in Shenzhen, China, 2013–2017. J Infect. 2019;79(4):389–399. doi: 10.1016/j.jinf.2019.07.010. [DOI] [PubMed] [Google Scholar]
  • 47.Hu Y, Lu S, Song Z, Wang W, Hao P, Li J, Zhang X, Yen HL, Shi B, Li T, Guan W, Xu L, Liu Y, Wang S, Zhang X, Tian D, Zhu Z, He J, Huang K, Chen H, Zheng L, Li X, Ping J, Kang B, Xi X, Zha L, Li Y, Zhang Z, Peiris M, Yuan Z. Association between adverse clinical outcome in human disease caused by novel influenza A H7N9 virus and sustained viral shedding and emergence of antiviral resistance. Lancet. 2013;381(9885):2273–2279. doi: 10.1016/S0140-6736(13)61125-3. [DOI] [PubMed] [Google Scholar]
  • 48.Dai J, Zhou X, Dong D, Liu Y, Gu Q, Zhu B, Wu C, Cai H. Human infection with a novel avian-origin influenza A (H7N9) virus: serial chest radiographic and CT findings. Chin Med J (Engl) 2014;127(12):2206–2211. [PubMed] [Google Scholar]
  • 49.Watanabe T, Kiso M, Fukuyama S, Nakajima N, Imai M, Yamada S, Murakami S, Yamayoshi S, Iwatsuki-Horimoto K, Sakoda Y, Takashita E, McBride R, Noda T, Hatta M, Imai H, Zhao D, Kishida N, Shirakura M, de Vries RP, Shichinohe S, Okamatsu M, Tamura T, Tomita Y, Fujimoto N, Goto K, Katsura H, Kawakami E, Ishikawa I, Watanabe S, Ito M, Sakai-Tagawa Y, Sugita Y, Uraki R, Yamaji R, Eisfeld AJ, Zhong G, Fan S, Ping J, Maher EA, Hanson A, Uchida Y, Saito T, Ozawa M, Neumann G, Kida H, Odagiri T, Paulson JC, Hasegawa H, Tashiro M, Kawaoka Y. Characterization of H7N9 influenza A viruses isolated from humans. Nature. 2013;501(7468):551–555. doi: 10.1038/nature12392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Zhang Q, Shi J, Deng G, Guo J, Zeng X, He X, Kong H, Gu C, Li X, Liu J, Wang G, Chen Y, Liu L, Liang L, Li Y, Fan J, Wang J, Li W, Guan L, Li Q, Yang H, Chen P, Jiang L, Guan Y, Xin X, Jiang Y, Tian G, Wang X, Qiao C, Li C, Bu Z, Chen H. H7N9 influenza viruses are transmissible in ferrets by respiratory droplet. Science. 2013;341(6144):410–414. doi: 10.1126/science.1240532. [DOI] [PubMed] [Google Scholar]
  • 51.OIE. Update on avian influenza in animals (types H5 and H7). https://www.oie.int/en/animal-health-in-the-world/update-on-avian-influenza. Updated October 22, 2020 (accessed November 15, 2020)
  • 52.Imai M, Watanabe T, Kiso M, Nakajima N, Yamayoshi S, Iwatsuki-Horimoto K, Hatta M, Yamada S, Ito M, Sakai-Tagawa Y, Shirakura M, Takashita E, Fujisaki S, McBride R, Thompson AJ, Takahashi K, Maemura T, Mitake H, Chiba S, Zhong G, Fan S, Oishi K, Yasuhara A, Takada K, Nakao T, Fukuyama S, Yamashita M, Lopes TJS, Neumann G, Odagiri T, Watanabe S, Shu Y, Paulson JC, Hasegawa H, Kawaoka Y. A highly pathogenic avian H7N9 influenza virus isolated from a human is lethal in some ferrets infected via respiratory droplets. Cell Host Microbe. 2017;22(5):615–626.e8. doi: 10.1016/j.chom.2017.09.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 53.Sun X, Belser JA, Pappas C, Pulit-Penaloza JA, Brock N, Zeng H, Creager HM, Le S, Wilson M, Lewis A, Stark TJ, Shieh WJ, Barnes J, Tumpey TM, Maines TR. Risk assessment of fifth-wave H7N9 influenza A viruses in mammalian models. J Virol. 2018;93(1):e01740–18. doi: 10.1128/JVI.01740-18. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Shi J, Deng G, Kong H, Gu C, Ma S, Yin X, Zeng X, Cui P, Chen Y, Yang H, Wan X, Wang X, Liu L, Chen P, Jiang Y, Liu J, Guan Y, Suzuki Y, Li M, Qu Z, Guan L, Zang J, Gu W, Han S, Song Y, Hu Y, Wang Z, Gu L, Yang W, Liang L, Bao H, Tian G, Li Y, Qiao C, Jiang L, Li C, Bu Z, Chen H. H7N9 virulent mutants detected in chickens in China pose an increased threat to humans. Cell Res. 2017;27(12):1409–1421. doi: 10.1038/cr.2017.129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 55.Bao L, Bi Y, Wong G, Qi W, Li F, Lv Q, Wang L, Liu F, Yang Y, Zhang C, Liu WJ, Quan C, Jia W, Liu Y, Liu W, Liao M, Gao GF, Qin C. Diverse biological characteristics and varied virulence of H7N9 from wave 5. Emerg Microbes Infect. 2019;8(1):94–102. doi: 10.1080/22221751.2018.1560234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Song W, Wang P, Mok BW, Lau SY, Huang X, Wu WL, Zheng M, Wen X, Yang S, Chen Y, Li L, Yuen KY, Chen H. The K526R substitution in viral protein PB2 enhances the effects of E627K on influenza virus replication. Nat Commun. 2014;5(1):5509. doi: 10.1038/ncomms6509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57.Mok CK, Lee HH, Lestra M, Nicholls JM, Chan MC, Sia SF, Zhu H, Poon LL, Guan Y, Peiris JS. 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. 2014;88(6):3568–3576. doi: 10.1128/JVI.02740-13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58.Xiao C, Ma W, Sun N, Huang L, Li Y, Zeng Z, Wen Y, Zhang Z, Li H, Li Q, Yu Y, Zheng Y, Liu S, Hu P, Zhang X, Ning Z, Qi W, Liao M. PB2-588V promotes the mammalian adaptation of H10N8, H7N9 and H9N2 avian influenza viruses. Sci Rep. 2016;6(1):19474. doi: 10.1038/srep19474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 59.Liu WJ, Li J, Zou R, Pan J, Jin T, Li L, Liu P, Zhao Y, Yu X, Wang H, Liu G, Jiang H, Bi Y, Liu L, Yuen KY, Liu Y, Gao GF. Dynamic PB2-E627K substitution of influenza H7N9 virus indicates the in vivo genetic tuning and rapid host adaptation. Proc Natl Acad Sci U S A. 2020;117(38):23807–23814. doi: 10.1073/pnas.2013267117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60.Bi Y, Xiao H, Chen Q, Wu Y, Fu L, Quan C, Wong G, Liu J, Haywood J, Liu Y, Zhou B, Yan J, Liu W, Gao GF. Changes in the length of the neuraminidase stalk region impact H7N9 virulence in mice. J Virol. 2016;90(4):2142–2149. doi: 10.1128/JVI.02553-15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 61.de Graaf M, Fouchier RA. Role of receptor binding specificity in influenza A virus transmission and pathogenesis. EMBO J. 2014;33(8):823–841. doi: 10.1002/embj.201387442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 62.Wiley DC, Skehel JJ. The structure and function of the hemagglutinin membrane glycoprotein of influenza virus. Annu Rev Biochem. 1987;56(1):365–394. doi: 10.1146/annurev.bi.56.070187.002053. [DOI] [PubMed] [Google Scholar]
  • 63.Shi Y, Wu Y, Zhang W, Qi J, Gao GF. Enabling the ‘host jump’: structural determinants of receptor-binding specificity in influenza A viruses. Nat Rev Microbiol. 2014;12(12):822–831. doi: 10.1038/nrmicro3362. [DOI] [PubMed] [Google Scholar]
  • 64.Sun X, Shi Y, Lu X, He J, Gao F, Yan J, Qi J, Gao GF. Bat-derived influenza hemagglutinin H17 does not bind canonical avian or human receptors and most likely uses a unique entry mechanism. Cell Rep. 2013;3(3):769–778. doi: 10.1016/j.celrep.2013.01.025. [DOI] [PubMed] [Google Scholar]
  • 65.Wu Y, Wu Y, Tefsen B, Shi Y, Gao GF. Bat-derived influenza-like viruses H17N10 and H18N11. Trends Microbiol. 2014;22(4):183–191. doi: 10.1016/j.tim.2014.01.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 66.Taubenberger JK, Kash JC. Influenza virus evolution, host adaptation, and pandemic formation. Cell Host Microbe. 2010;7(6):440–451. doi: 10.1016/j.chom.2010.05.009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 67.Xiong XL, McCauley JW, Steinhauer DA. Receptor binding properties of the influenza virus hemagglutinin as a determinant of host range. Curr Top Microbiol Immunol. 2014;385:63–91. doi: 10.1007/82_2014_423. [DOI] [PubMed] [Google Scholar]
  • 68.Bao CJ, Cui LB, Zhou MH, Hong L, Gao GF, Wang H. Live-animal markets and influenza A (H7N9) virus infection. N Engl J Med. 2013;368(24):2337–2339. doi: 10.1056/NEJMc1306100. [DOI] [PubMed] [Google Scholar]
  • 69.Vijaykrishna D, Deng YM, Grau ML, Kay M, Suttie A, Horwood PF, Kalpravidh W, Claes F, Osbjer K, Dussart P, Barr IG, Karlsson EA. Emergence of influenza A (H7N4) virus, Cambodia. Emerg Infect Dis. 2019;25(10):1988–1991. doi: 10.3201/eid2510.190506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 70.Xu Y, Peng R, Zhang W, Qi J, Song H, Liu S, Wang H, Wang M, Xiao H, Fu L, Fan Z, Bi Y, Yan J, Shi Y, Gao GF. Avian-to-human receptor-binding adaptation of avian H7N9 influenza virus hemagglutinin. Cell Rep. 2019;29(8):2217–2228.e5. doi: 10.1016/j.celrep.2019.10.047. [DOI] [PubMed] [Google Scholar]
  • 71.Shi Y, Zhang W, Wang F, Qi J, Wu Y, Song H, Gao F, Bi Y, Zhang Y, Fan Z, Qin C, Sun H, Liu J, Haywood J, Liu W, Gong W, Wang D, Shu Y, Wang Y, Yan J, Gao GF. Structures and receptor binding of hemagglutinins from human-infecting H7N9 influenza viruses. Science. 2013;342(6155):243–247. doi: 10.1126/science.1242917. [DOI] [PubMed] [Google Scholar]
  • 72.Xiong X, Martin SR, Haire LF, Wharton SA, Daniels RS, Bennett MS, McCauley JW, Collins PJ, Walker PA, Skehel JJ, Gamblin SJ. Receptor binding by an H7N9 influenza virus from humans. Nature. 2013;499(7459):496–499. doi: 10.1038/nature12372. [DOI] [PubMed] [Google Scholar]
  • 73.Kageyama T, Fujisaki S, Takashita E, Xu H, Yamada S, Uchida Y, Neumann G, Saito T, Kawaoka Y, Tashiro M. Genetic analysis of novel avian A (H7N9) influenza viruses isolated from patients in China, February to April 2013. Euro Surveill. 2013;18(15):20453. doi: 10.2807/ese.18.15.20453-en. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 74.de Vries RP, Peng W, Grant OC, Thompson AJ, Zhu X, Bouwman KM, de la Pena ATT, van Breemen MJ, Ambepitiya Wickrama-singhe IN, de Haan CAM, Yu W, McBride R, Sanders RW, Woods RJ, Verheije MH, Wilson IA, Paulson JC. Three mutations switch H7N9 influenza to human-type receptor specificity. PLoS Pathog. 2017;13(6):e1006390. doi: 10.1371/journal.ppat.1006390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 75.Wang Z, Zhang A, Wan Y, Liu X, Qiu C, Xi X, Ren Y, Wang J, Dong Y, Bao M, Li L, Zhou M, Yuan S, Sun J, Zhu Z, Chen L, Li Q, Zhang Z, Zhang X, Lu S, Doherty PC, Kedzierska K, Xu J. Early hypercytokinemia is associated with interferon-induced transmembrane protein-3 dysfunction and predictive of fatal H7N9 infection. Proc Natl Acad Sci USA. 2014;111(2):769–774. doi: 10.1073/pnas.1321748111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 76.Guo J, Huang F, Liu J, Chen Y, Wang W, Cao B, Zou Z, Liu S, Pan J, Bao C, Zeng M, Xiao H, Gao H, Yang S, Zhao Y, Liu Q, Zhou H, Zhu J, Liu X, Liang W, Yang Y, Zheng S, Yang J, Diao H, Su K, Shao L, Cao H, Wu Y, Zhao M, Tan S, Li H, Xu X, Wang C, Zhang J, Wang L, Wang J, Xu J, Li D, Zhong N, Cao X, Gao GF, Li L, Jiang C. The serum profile of hypercytokinemia factors identified in H7N9-Infected patients can predict fatal outcomes. Sci Rep. 2015;5(1):10942. doi: 10.1038/srep10942. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 77.Huang F, Guo J, Zou Z, Liu J, Cao B, Zhang S, Li H, Wang W, Sheng M, Liu S, Pan J, Bao C, Zeng M, Xiao H, Qian G, Hu X, Chen Y, Chen Y, Zhao Y, Liu Q, Zhou H, Zhu J, Gao H, Yang S, Liu X, Zheng S, Yang J, Diao H, Cao H, Wu Y, Zhao M, Tan S, Guo D, Zhao X, Ye Y, Wu W, Xu Y, Penninger JM, Li D, Gao GF, Jiang C, Li L. Angiotensin II plasma levels are linked to disease severity and predict fatal outcomes in H7N9-infected patients. Nat Commun. 2014;5(1):3595. doi: 10.1038/ncomms4595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 78.Chen Y, Liang W, Yang S, Wu N, Gao H, Sheng J, Yao H, Wo J, Fang Q, Cui D, Li Y, Yao X, Zhang Y, Wu H, Zheng S, Diao H, Xia S, Zhang Y, Chan KH, Tsoi HW, Teng JL, Song W, Wang P, Lau SY, Zheng M, Chan JF, To KK, Chen H, Li L, Yuen KY. Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genome. Lancet. 2013;381(9881):1916–1925. doi: 10.1016/S0140-6736(13)60903-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 79.Bi Y, Liu J, Xiong H, Zhang Y, Liu D, Liu Y, Gao GF, Wang B. A new reassortment of influenza A (H7N9) virus causing human infection in Beijing, 2014. Sci Rep. 2016;6(1):26624. doi: 10.1038/srep26624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 80.Chi Y, Zhu Y, Wen T, Cui L, Ge Y, Jiao Y, Wu T, Ge A, Ji H, Xu K, Bao C, Zhu Z, Qi X, Wu B, Shi Z, Tang F, Xing Z, Zhou M. Cytokine and chemokine levels in patients infected with the novel avian influenza A (H7N9) virus in China. J Infect Dis. 2013;208(12):1962–1967. doi: 10.1093/infdis/jit440. [DOI] [PubMed] [Google Scholar]
  • 81.Zhou J, Wang D, Gao R, Zhao B, Song J, Qi X, Zhang Y, Shi Y, Yang L, Zhu W, Bai T, Qin K, Lan Y, Zou S, Guo J, Dong J, Dong L, Zhang Y, Wei H, Li X, Lu J, Liu L, Zhao X, Li X, Huang W, Wen L, Bo H, Xin L, Chen Y, Xu C, Pei Y, Yang Y, Zhang X, Wang S, Feng Z, Han J, Yang W, Gao GF, Wu G, Li D, Wang Y, Shu Y. Biological features of novel avian influenza A (H7N9) virus. Nature. 2013;499(7459):500–503. doi: 10.1038/nature12379. [DOI] [PubMed] [Google Scholar]
  • 82.Bi Y, Tan S, Yang Y, Wong G, Zhao M, Zhang Q, Wang Q, Zhao X, Li L, Yuan J, Li H, Li H, Xu W, Shi W, Quan C, Zou R, Li J, Zheng H, Yang L, Liu WJ, Liu D, Wang H, Qin Y, Liu L, Jiang C, Liu W, Lu L, Gao GF, Liu Y. Clinical and immunological characteristics of human infections with H5N6 avian influenza virus. Clin Infect Dis. 2019;68(7):1100–1109. doi: 10.1093/cid/ciy681. [DOI] [PubMed] [Google Scholar]
  • 83.Chen Y, Li X, Tian L, Zheng S, Yang S, Dong Y, Wang Y, Cui D, Liu X, Liang W, Chen H, Li L. Dynamic behavior of lymphocyte subgroups correlates with clinical outcomes in human H7N9 infection. J Infect. 2014;69(4):358–365. doi: 10.1016/j.jinf.2014.05.006. [DOI] [PubMed] [Google Scholar]
  • 84.Diao H, Cui G, Wei Y, Chen J, Zuo J, Cao H, Chen Y, Yao H, Tian Z, Li L. Severe H7N9 infection is associated with decreased antigen-presenting capacity of CD14+ cells. PLoS One. 2014;9(3):e92823. doi: 10.1371/journal.pone.0092823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 85.Wang Z, Wan Y, Qiu C, Quiñones-Parra S, Zhu Z, Loh L, Tian D, Ren Y, Hu Y, Zhang X, Thomas PG, Inouye M, Doherty PC, Kedzierska K, Xu J. Recovery from severe H7N9 disease is associated with diverse response mechanisms dominated by CD8+ T cells. Nat Commun. 2015;6(1):6833. doi: 10.1038/ncomms7833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 86.Wang Z, Zhu L, Nguyen THO, Wan Y, Sant S, Quiñones-Parra SM, Crawford JC, Eltahla AA, Rizzetto S, Bull RA, Qiu C, Koutsakos M, Clemens EB, Loh L, Chen T, Liu L, Cao P, Ren Y, Kedzierski L, Kotsimbos T, McCaw JM, La Gruta NL, Turner SJ, Cheng AC, Luciani F, Zhang X, Doherty PC, Thomas PG, Xu J, Kedzierska K. Clonally diverse CD38+HLA-DR+CD8+ T cells persist during fatal H7N9 disease. Nat Commun. 2018;9(1):824. doi: 10.1038/s41467-018-03243-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 87.Hou D, Ying T, Wang L, Chen C, Lu S, Wang Q, Seeley E, Xu J, Xi X, Li T, Liu J, Tang X, Zhang Z, Zhou J, Bai C, Wang C, Byrne-Steele M, Qu J, Han J, Song Y. Immune repertoire diversity correlated with mortality in avian influenza A (H7N9) virus infected patients. Sci Rep. 2016;6(1):33843. doi: 10.1038/srep33843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 88.Chen J, Cui G, Lu C, Ding Y, Gao H, Zhu Y, Wei Y, Wang L, Uede T, Li L, Diao H. Severe infection with avian influenza A virus is associated with delayed immune recovery in survivors. Medicine (Baltimore) 2016;95(5):e2606. doi: 10.1097/MD.0000000000002606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 89.Zhao M, Chen J, Tan S, Dong T, Jiang H, Zheng J, Quan C, Liao Q, Zhang H, Wang X, Wang Q, Bi Y, Liu F, Feng L, Horby PW, Klenerman P, Gao GF, Liu WJ, Yu H. Prolonged evolution of virus-specific memory T cell immunity after severe avian influenza A (H7N9) virus infection. J Virol. 2018;92(17):e01024–18. doi: 10.1128/JVI.01024-18. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 90.Ma MJ, Wang XX, Wu MN, Wang XJ, Bao CJ, Zhang HJ, Yang Y, Xu K, Wang GL, Zhao M, Cheng W, Chen WJ, Zhang WH, Fang LQ, Liu WJ, Chen EF, Cao WC. Characterization of antibody and memory T-cell response in H7N9 survivors: a cross-sectional analysis. Clin Microbiol Infect. 2020;26(2):247–254. doi: 10.1016/j.cmi.2019.06.013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 91.van de Sandt CE, Kreijtz JH, de Mutsert G, Geelhoed-Mieras MM, Hillaire ML, Vogelzang-van Trierum SE, Osterhaus AD, Fouchier RA, Rimmelzwaan GF. Human cytotoxic T lymphocytes directed to seasonal influenza A viruses cross-react with the newly emerging H7N9 virus. J Virol. 2014;88(3):1684–1693. doi: 10.1128/JVI.02843-13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 92.Liu WJ, Tan S, Zhao M, Quan C, Bi Y, Wu Y, Zhang S, Zhang H, Xiao H, Qi J, Yan J, Liu W, Yu H, Shu Y, Wu G, Gao GF. Cross-immunity against avian influenza A (H7N9) virus in the healthy population is affected by antigenicity-dependent substitutions. J Infect Dis. 2016;214(12):1937–1946. doi: 10.1093/infdis/jiw471. [DOI] [PubMed] [Google Scholar]
  • 93.Quiñones-Parra S, Grant E, Loh L, Nguyen TH, Campbell KA, Tong SY, Miller A, Doherty PC, Vijaykrishna D, Rossjohn J, Gras S, Kedzierska K. Preexisting CD8+ T-cell immunity to the H7N9 influenza A virus varies across ethnicities. Proc Natl Acad Sci USA. 2014;111(3):1049–1054. doi: 10.1073/pnas.1322229111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 94.Liu J, Wu B, Zhang S, Tan S, Sun Y, Chen Z, Qin Y, Sun M, Shi G, Wu Y, Sun M, Liu N, Ning K, Ma Y, Gao B, Yan J, Zhu F, Wang H, Gao GF. Conserved epitopes dominate cross- CD8+ T-cell responses against influenza A H1N1 virus among Asian populations. Eur J Immunol. 2013;43(8):2055–2069. doi: 10.1002/eji.201343417. [DOI] [PubMed] [Google Scholar]
  • 95.Zhao M, Liu K, Luo J, Tan S, Quan C, Zhang S, Chai Y, Qi J, Li Y, Bi Y, Xiao H, Wong G, Zhou J, Jiang T, Liu W, Yu H, Yan J, Liu Y, Shu Y, Wu G, Wu A, Gao GF, Liu WJ. Heterosubtypic protections against human-infecting avian influenza viruses correlate to biased cross-T-cell responses. MBio. 2018;9(4):e01408–18. doi: 10.1128/mBio.01408-18. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 96.Duan S, Meliopoulos VA, McClaren JL, Guo XZ, Sanders CJ, Smallwood HS, Webby RJ, Schultz-Cherry SL, Doherty PC, Thomas PG. Diverse heterologous primary infections radically alter immunodominance hierarchies and clinical outcomes following H7N9 influenza challenge in mice. PLoS Pathog. 2015;11(2):e1004642. doi: 10.1371/journal.ppat.1004642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 97.McMaster SR, Gabbard JD, Koutsonanos DG, Compans RW, Tripp RA, Tompkins SM, Kohlmeier JE. Memory T cells generated by prior exposure to influenza cross react with the novel H7N9 influenza virus and confer protective heterosubtypic immunity. PLoS One. 2015;10(2):e0115725. doi: 10.1371/journal.pone.0115725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 98.Chen Z, Wang J, Bao L, Guo L, Zhang W, Xue Y, Zhou H, Xiao Y, Wang J, Wu F, Deng Y, Qin C, Jin Q. Human monoclonal antibodies targeting the haemagglutinin glycoprotein can neutralize H7N9 influenza virus. Nat Commun. 2015;6(1):6714. doi: 10.1038/ncomms7714. [DOI] [PubMed] [Google Scholar]
  • 99.Wang J, Chen Z, Bao L, Zhang W, Xue Y, Pang X, Zhang X, Qin C, Jin Q. Characterization of two human monoclonal antibodies neutralizing influenza A H7N9 viruses. J Virol. 2015;89(17):9115–9118. doi: 10.1128/JVI.01295-15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 100.Huang KA, Rijal P, Jiang H, Wang B, Schimanski L, Dong T, Liu YM, Chang P, Iqbal M, Wang MC, Chen Z, Song R, Huang CC, Yang JH, Qi J, Lin TY, Li A, Powell TJ, Jan JT, Ma C, Gao GF, Shi Y, Townsend AR. Structure-function analysis of neutralizing antibodies to H7N9 influenza from naturally infected humans. Nat Microbiol. 2019;4(2):306–315. doi: 10.1038/s41564-018-0303-7. [DOI] [PubMed] [Google Scholar]
  • 101.Li M, Chen L, Wang Q, Hao M, Zhang X, Liu L, Yu X, Yang C, Xu J, Chen J, Gong R. A cross-reactive human monoclonal antibody targets the conserved H7 antigenic site A from fifth wave H7N9-infected humans. Antiviral Res. 2019;170:104556. doi: 10.1016/j.antiviral.2019.104556. [DOI] [PubMed] [Google Scholar]
  • 102.Li J, Yang Y, Wang M, Ren X, Yang Z, Liu L, Zhang G, Chen Q, Yang W, Chen YH, Wan X. Rapid isolation of a potent human antibody against H7N9 influenza virus from an infected patient. Antiviral Res. 2019;170:104564. doi: 10.1016/j.antiviral.2019.104564. [DOI] [PubMed] [Google Scholar]
  • 103.Henry Dunand CJ, Leon PE, Huang M, Choi A, Chromikova V, Ho IY, Tan GS, Cruz J, Hirsh A, Zheng NY, Mullarkey CE, Ennis FA, Terajima M, Treanor JJ, Topham DJ, Subbarao K, Palese P, Krammer F, Wilson PC. Both neutralizing and non-neutralizing human H7N9 influenza vaccine-induced monoclonal antibodies confer protection. Cell Host Microbe. 2016;19(6):800–813. doi: 10.1016/j.chom.2016.05.014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 104.Thornburg NJ, Zhang H, Bangaru S, Sapparapu G, Kose N, Lampley RM, Bombardi RG, Yu Y, Graham S, Branchizio A, Yoder SM, Rock MT, Creech CB, Edwards KM, Lee D, Li S, Wilson IA, García-Sastre A, Albrecht RA, Crowe JE., Jr. H7N9 influenza virus neutralizing antibodies that possess few somatic mutations. J Clin Invest. 2016;126(4):1482–1494. doi: 10.1172/JCI85317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 105.Tan GS, Leon PE, Albrecht RA, Margine I, Hirsh A, Bahl J, Krammer F. Broadly-reactive neutralizing and non-neutralizing antibodies directed against the H7 influenza virus hemagglutinin reveal divergent mechanisms of protection. PLoS Pathog. 2016;12(4):e1005578. doi: 10.1371/journal.ppat.1005578. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 106.Schmeisser F, Vasudevan A, Verma S, Wang W, Alvarado E, Weiss C, Atukorale V, Meseda C, Weir JP. Antibodies to antigenic site A of influenza H7 hemagglutinin provide protection against H7N9 challenge. PLoS One. 2015;10(1):e0117108. doi: 10.1371/journal.pone.0117108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 107.Stadlbauer D, Amanat F, Strohmeier S, Nachbagauer R, Krammer F. Cross-reactive mouse monoclonal antibodies raised against the hemagglutinin of A/Shanghai/1/2013 (H7N9) protect against novel H7 virus isolates in the mouse model. Emerg Microbes Infect. 2018;7(1):110. doi: 10.1038/s41426-018-0115-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 108.He F, Kumar SR, Syed Khader SM, Tan Y, Prabakaran M, Kwang J. Effective intranasal therapeutics and prophylactics with monoclonal antibody against lethal infection of H7N7 influenza virus. Antiviral Res. 2013;100(1):207–214. doi: 10.1016/j.antiviral.2013.08.003. [DOI] [PubMed] [Google Scholar]
  • 109.Chen C, Liu L, Xiao Y, Cui S, Wang J, Jin Q. Structural insight into a human neutralizing antibody against influenza virus H7N9. J Virol. 2018;92(5):e01850–17. doi: 10.1128/JVI.01850-17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 110.Yu F, Song H, Wu Y, Chang SY, Wang L, Li W, Hong B, Xia S, Wang C, Khurana S, Feng Y, Wang Y, Sun Z, He B, Hou D, Manischewitz J, King LR, Song Y, Min JY, Golding H, Ji X, Lu L, Jiang S, Dimitrov DS, Ying T. A potent germline-like human monoclonal antibody targets a pH-sensitive epitope on H7N9 influenza hemagglutinin. Cell Host Microbe. 2017;22(4):471–483.e5. doi: 10.1016/j.chom.2017.08.011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 111.Hong M, Lee PS, Hoffman RM, Zhu X, Krause JC, Laursen NS, Yoon SI, Song L, Tussey L, Crowe JE, Jr., Ward AB, Wilson IA. Antibody recognition of the pandemic H1N1 Influenza virus hemagglutinin receptor binding site. J Virol. 2013;87(22):12471–12480. doi: 10.1128/JVI.01388-13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 112.Whittle JRR, Zhang R, Khurana S, King LR, Manischewitz J, Golding H, Dormitzer PR, Haynes BF, Walter EB, Moody MA, Kepler TB, Liao HX, Harrison SC. Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin. Proc Natl Acad Sci USA. 2011;108(34):14216–14221. doi: 10.1073/pnas.1111497108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 113.Xu R, Krause JC, McBride R, Paulson JC, Crowe JE, Jr., Wilson IA. A recurring motif for antibody recognition of the receptor-binding site of influenza hemagglutinin. Nat Struct Mol Biol. 2013;20(3):363–370. doi: 10.1038/nsmb.2500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 114.Laursen NS, Wilson IA. Broadly neutralizing antibodies against influenza viruses. Antiviral Res. 2013;98(3):476–483. doi: 10.1016/j.antiviral.2013.03.021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 115.Ekiert DC, Kashyap AK, Steel J, Rubrum A, Bhabha G, Khayat R, Lee JH, Dillon MA, O’Neil RE, Faynboym AM, Horowitz M, Horowitz L, Ward AB, Palese P, Webby R, Lerner RA, Bhatt RR, Wilson IA. Cross-neutralization of influenza A viruses mediated by a single antibody loop. Nature. 2012;489(7417):526–532. doi: 10.1038/nature11414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 116.Lee PS, Ohshima N, Stanfield RL, Yu W, Iba Y, Okuno Y, Kurosawa Y, Wilson IA. Receptor mimicry by antibody F045-092 facilitates universal binding to the H3 subtype of influenza virus. Nat Commun. 2014;5(1):3614. doi: 10.1038/ncomms4614. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 117.Lee PS, Yoshida R, Ekiert DC, Sakai N, Suzuki Y, Takada A, Wilson IA. Heterosubtypic antibody recognition of the influenza virus hemagglutinin receptor binding site enhanced by avidity. Proc Natl Acad Sci USA. 2012;109(42):17040–17045. doi: 10.1073/pnas.1212371109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 118.Yoshida R, Igarashi M, Ozaki H, Kishida N, Tomabechi D, Kida H, Ito K, Takada A. Cross-protective potential of a novel monoclonal antibody directed against antigenic site B of the hemagglutinin of influenza A viruses. PLoS Pathog. 2009;5(3):e1000350. doi: 10.1371/journal.ppat.1000350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 119.Bangaru S, Lang S, Schotsaert M, Vanderven HA, Zhu X, Kose N, Bombardi R, Finn JA, Kent SJ, Gilchuk P, Gilchuk I, Turner HL, Garcia-Sastre A, Li S, Ward AB, Wilson IA, Crowe JE., Jr. A site of vulnerability on the influenza virus hemagglutinin head domain trimer interface. Cell. 2019;177(5):1136–1152.e18. doi: 10.1016/j.cell.2019.04.011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 120.Okuno Y, Isegawa Y, Sasao F, Ueda S. A common neutralizing epitope conserved between the hemagglutinins of influenza A virus H1 and H2 strains. J Virol. 1993;67(5):2552–2558. doi: 10.1128/jvi.67.5.2552-2558.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 121.Sedeyn K, Saelens X. New antibody-based prevention and treatment options for influenza. Antiviral Res. 2019;170:104562. doi: 10.1016/j.antiviral.2019.104562. [DOI] [PubMed] [Google Scholar]
  • 122.Xiao H, Guo T, Yang M, Qi J, Huang C, Hong Y, Gu J, Pang X, Liu WJ, Peng R, McCauley J, Bi Y, Li S, Feng J, Zhang H, Zhang X, Lu X, Yan J, Chen L, Shi Y, Chen W, Gao GF. Light chain modulates heavy chain conformation to change protection profile of monoclonal antibodies against influenza A viruses. Cell Discov. 2019;5(1):21. doi: 10.1038/s41421-019-0086-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 123.Dreyfus C, Laursen NS, Kwaks T, Zuijdgeest D, Khayat R, Ekiert DC, Lee JH, Metlagel Z, Bujny MV, Jongeneelen M, van der Vlugt R, Lamrani M, Korse HJ, Geelen E, Sahin Ö, Sieuwerts M, Brakenhoff JP, Vogels R, Li OT, Poon LL, Peiris M, Koudstaal W, Ward AB, Wilson IA, Goudsmit J, Friesen RH. Highly conserved protective epitopes on influenza B viruses. Science. 2012;337(6100):1343–1348. doi: 10.1126/science.1222908. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 124.Eichelberger MC, Wan H. Influenza neuraminidase as a vaccine antigen. Curr Top Microbiol Immunol. 2015;386:275–299. doi: 10.1007/82_2014_398. [DOI] [PubMed] [Google Scholar]
  • 125.Wilson JR, Guo Z, Reber A, Kamal RP, Music N, Gansebom S, Bai Y, Levine M, Carney P, Tzeng WP, Stevens J, York IA. An influenza A virus (H7N9) anti-neuraminidase monoclonal antibody with prophylactic and therapeutic activity in vivo. Antiviral Res. 2016;135:48–55. doi: 10.1016/j.antiviral.2016.10.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 126.Li J, Yu X, Pu X, Xie L, Sun Y, Xiao H, Wang F, Din H, Wu Y, Liu D, Zhao G, Liu J, Pan J. Environmental connections of novel avian-origin H7N9 influenza virus infection and virus adaptation to the human. Sci China Life Sci. 2013;56(6):485–492. doi: 10.1007/s11427-013-4491-3. [DOI] [PubMed] [Google Scholar]
  • 127.Wan H, Qi L, Gao J, Couzens LK, Jiang L, Gao Y, Sheng ZM, Fong S, Hahn M, Khurana S, Taubenberger JK, Eichelberger MC. Comparison of the efficacy of N9 neuraminidase-specific monoclonal antibodies against influenza A (H7N9) virus infection. J Virol. 2018;92(4):e01588–17. doi: 10.1128/JVI.01588-17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 128.Gilchuk IM, Bangaru S, Gilchuk P, Irving RP, Kose N, Bombardi RG, Thornburg NJ, Creech CB, Edwards KM, Li S, Turner HL, Yu W, Zhu X, Wilson IA, Ward AB, Crowe JE., Jr. Influenza H7N9 virus neuraminidase-specific human monoclonal antibodies inhibit viral egress and protect from lethal influenza infection in mice. Cell Host Microbe. 2019;26(6):715–728.e8. doi: 10.1016/j.chom.2019.10.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 129.Rijal P, Wang BB, Tan TK, Schimanski L, Janesch P, Dong T, McCauley JW, Daniels RS, Townsend AR, Huang KA. Broadly inhibiting anti-neuraminidase monoclonal antibodies induced by trivalent influenza vaccine and H7N9 infection in humans. J Virol. 2020;94(4):e01182–19. doi: 10.1128/JVI.01182-19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 130.Jiang H, Peng W, Qi J, Chai Y, Song H, Bi Y, Rijal P, Wang H, Oladejo BO, Liu J, Shi Y, Gao GF, Townsend AR, Wu Y. Structure-based modification of an anti-neuraminidase human antibody restores protection efficacy against the drifted influenza virus. mBio. 2020;11(5):02315–20. doi: 10.1128/mBio.02315-20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 131.Chen YQ, Wohlbold TJ, Zheng NY, Huang M, Huang Y, Neu KE, Lee J, Wan H, Rojas KT, Kirkpatrick E, Henry C, Palm AE, Stamper CT, Lan LY, Topham DJ, Treanor J, Wrammert J, Ahmed R, Eichelberger MC, Georgiou G, Krammer F, Wilson PC. Influenza infection in humans induces broadly cross-reactive and protective neuraminidase-reactive antibodies. Cell. 2018;173(2):417–429.e10. doi: 10.1016/j.cell.2018.03.030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 132.Tang J, Wang D. Research progress in human infection with avian influenza H7N9 virus. Sci China Life Sci. 2017;60(12):1299–1306. doi: 10.1007/s11427-017-9221-4. [DOI] [PubMed] [Google Scholar]
  • 133.Isakova-Sivak I, Rudenko L. Tackling a novel lethal virus: a focus on H7N9 vaccine development. Expert Rev Vaccines. 2017;16(7):709–721. doi: 10.1080/14760584.2017.1333907. [DOI] [PubMed] [Google Scholar]
  • 134.Wodal W, Schwendinger MG, Savidis-Dacho H, Crowe BA, Hohenadl C, Fritz R, Brhl P, Portsmouth D, Karner-Pichl A, Balta D, Grillberger L, Kistner O, Barrett PN, Howard MK. Immunogenicity and protective efficacy of a Vero cell culture-derived whole-virus H7N9 vaccine in mice and guinea pigs. PLoS One. 2015;10(2):e0113963. doi: 10.1371/journal.pone.0113963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 135.Chu DH, Sakoda Y, Nishi T, Hiono T, Shichinohe S, Okamatsu M, Kida H. Potency of an inactivated influenza vaccine prepared from A/duck/Mongolia/119/2008 (H7N9) against the challenge with A/Anhui/1/2013 (H7N9) Vaccine. 2014;32(28):3473–3479. doi: 10.1016/j.vaccine.2014.04.060. [DOI] [PubMed] [Google Scholar]
  • 136.No authors listed. Zoonotic influenza viruses: antigenic and genetic characteristics and development of candidate vaccine viruses for pandemic preparedness. Wkly Epidemiol Rec 2016; 91(42): 485–499 (in French) [PubMed]
  • 137.Seo SH, Kim HS. Inactivated antigen of the H7N9 influenza virus protects mice from its lethal infection. Viral Immunol. 2016;29(4):235–243. doi: 10.1089/vim.2015.0103. [DOI] [PubMed] [Google Scholar]
  • 138.Pan W, Han L, Dong Z, Niu X, Li Z, Bao L, Li C, Luo Q, Yang Z, Li X, Huang J, Feng L, Qin C, Zhong N, Chen L. Induction of neutralizing antibodies to influenza A virus H7N9 by inactivated whole virus in mice and nonhuman primates. Antiviral Res. 2014;107:1–5. doi: 10.1016/j.antiviral.2014.04.003. [DOI] [PubMed] [Google Scholar]
  • 139.Chia MY, Hu AY, Tseng YF, Weng TC, Lai CC, Lin JY, Chen PL, Wang YF, Chao SR, Chang JY, Hwang YS, Yeh CT, Yu CP, Chen YC, Su IJ, Lee MS. Evaluation of MDCK cell-derived influenza H7N9 vaccine candidates in ferrets. PLoS One. 2015;10(3):e0120793. doi: 10.1371/journal.pone.0120793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 140.Barría MI, Garrido JL, Stein C, Scher E, Ge Y, Engel SM, Kraus TA, Banach D, Moran TM. Localized mucosal response to intranasal live attenuated influenza vaccine in adults. J Infect Dis. 2013;207(1):115–124. doi: 10.1093/infdis/jis641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 141.Petukhova G, Naikhin A, Chirkova T, Donina S, Korenkov D, Rudenko L. Comparative studies of local antibody and cellular immune responses to influenza infection and vaccination with live attenuated reassortant influenza vaccine (LAIV) utilizing a mouse nasal-associated lymphoid tissue (NALT) separation method. Vaccine. 2009;27(19):2580–2587. doi: 10.1016/j.vaccine.2009.02.035. [DOI] [PubMed] [Google Scholar]
  • 142.Powell TJ, Strutt T, Reome J, Hollenbaugh JA, Roberts AD, Woodland DL, Swain SL, Dutton RW. Priming with cold-adapted influenza A does not prevent infection but elicits long-lived protection against supralethal challenge with heterosubtypic virus. J Immunol. 2007;178(2):1030–1038. doi: 10.4049/jimmunol.178.2.1030. [DOI] [PubMed] [Google Scholar]
  • 143.Tamura S, Tanimoto T, Kurata T. Mechanisms of broad cross-protection provided by influenza virus infection and their application to vaccines. Jpn J Infect Dis. 2005;58(4):195–207. [PubMed] [Google Scholar]
  • 144.Chirkova TV, Naykhin AN, Petukhova GD, Korenkov DA, Donina SA, Mironov AN, Rudenko LG. Memory T-cell immune response in healthy young adults vaccinated with live attenuated influenza A (H5N2) vaccine. Clin Vaccine Immunol. 2011;18(10):1710–1718. doi: 10.1128/CVI.05116-11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 145.He XS, Holmes TH, Zhang C, Mahmood K, Kemble GW, Lewis DB, Dekker CL, Greenberg HB, Arvin AM. Cellular immune responses in children and adults receiving inactivated or live attenuated influenza vaccines. J Virol. 2006;80(23):11756–11766. doi: 10.1128/JVI.01460-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 146.Hoft DF, Babusis E, Worku S, Spencer CT, Lottenbach K, Truscott SM, Abate G, Sakala IG, Edwards KM, Creech CB, Gerber MA, Bernstein DI, Newman F, Graham I, Anderson EL, Belshe RB. Live and inactivated influenza vaccines induce similar humoral responses, but only live vaccines induce diverse T-cell responses in young children. J Infect Dis. 2011;204(6):845–853. doi: 10.1093/infdis/jir436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 147.Isakova-Sivak I, Rudenko L. Safety, immunogenicity and infectivity of new live attenuated influenza vaccines. Expert Rev Vaccines. 2015;14(10):1313–1329. doi: 10.1586/14760584.2015.1075883. [DOI] [PubMed] [Google Scholar]
  • 148.Chen Z, Baz M, Lu J, Paskel M, Santos C, Subbarao K, Jin H, Matsuoka Y. Development of a high-yield live attenuated H7N9 influenza virus vaccine that provides protection against homologous and heterologous H7 wild-type viruses in ferrets. J Virol. 2014;88(12):7016–7023. doi: 10.1128/JVI.00100-14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 149.Yang X, Zhao J, Wang C, Duan Y, Zhao Z, Chen R, Zhang L, Xing L, Lai C, Zhang S, Wang X, Yang P. Immunization with a live attenuated H7N9 influenza vaccine protects mice against lethal challenge. PLoS One. 2015;10(4):e0123659. doi: 10.1371/journal.pone.0123659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 150.Kong H, Zhang Q, Gu C, Shi J, Deng G, Ma S, Liu J, Chen P, Guan Y, Jiang Y, Chen H. A live attenuated vaccine prevents replication and transmission of H7N9 virus in mammals. Sci Rep. 2015;5(1):11233. doi: 10.1038/srep11233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 151.Shcherbik S, Pearce N, Balish A, Jones J, Thor S, Davis CT, Pearce M, Tumpey T, Cureton D, Chen LM, Villanueva J, Bousse TL. Generation and characterization of live attenuated influenza A (H7N9) candidate vaccine virus based on Russian donor of attenuation. PLoS One. 2015;10(9):e0138951. doi: 10.1371/journal.pone.0138951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 152.Fries LF, Smith GE, Glenn GM. A recombinant viruslike particle influenza A (H7N9) vaccine. N Engl J Med. 2013;369(26):2564–2566. doi: 10.1056/NEJMc1313186. [DOI] [PubMed] [Google Scholar]
  • 153.Liu YV, Massare MJ, Pearce MB, Sun X, Belser JA, Maines TR, Creager HM, Glenn GM, Pushko P, Smith GE, Tumpey TM. Recombinant virus-like particles elicit protective immunity against avian influenza A (H7N9) virus infection in ferrets. Vaccine. 2015;33(18):2152–2158. doi: 10.1016/j.vaccine.2015.03.009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 154.Pillet S, Racine T, Nfon C, Di Lenardo TZ, Babiuk S, Ward BJ, Kobinger GP, Landry N. Plant-derived H7 VLP vaccine elicits protective immune response against H7N9 influenza virus in mice and ferrets. Vaccine. 2015;33(46):6282–6289. doi: 10.1016/j.vaccine.2015.09.065. [DOI] [PubMed] [Google Scholar]
  • 155.Feng L, Feng S, Chen T, Yang J, Lau YC, Peng Z, Li L, Wang X, Wong JYT, Qin Y, Bond HS, Zhang J, Fang VJ, Zheng J, Yang J, Wu P, Jiang H, He Y, Cowling BJ, Yu H, Shu Y, Lau EHY. Burden of influenza-associated outpatient influenza-like illness consultations in China, 2006–2015: a population-based study. Influenza Other Respir Viruses. 2020;14(2):162–172. doi: 10.1111/irv.12711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 156.Rasmussen SA, Redd SC. Using results from infectious disease modeling to improve the response to a potential H7N9 influenza pandemic. Clin Infect Dis. 2015;60(Suppl 1):S9–S10. doi: 10.1093/cid/civ090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 157.Qi X, Jiang D, Wang H, Zhuang D, Ma J, Fu J, Qu J, Sun Y, Yu S, Meng Y, Huang Y, Xia L, Li Y, Wang Y, Wang G, Xu K, Zhang Q, Wan M, Su X, Fu G, Gao GF. Calculating the burden of disease of avian-origin H7N9 infections in China. BMJ Open. 2014;4(1):e004189. doi: 10.1136/bmjopen-2013-004189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 158.Huo X, Chen LL, Hong L, Xiang LH, Tang FY, Chen SH, Gao Q, Chen C, Dai QG, Sun CW, Xu K, Dai WJ, Qi X, Li CC, Yu HY, Zhou Y, Huang HD, Pan XY, Xu CS, Zhou MH, Bao CJ. Economic burden and its associated factors of hospitalized patients infected with A (H7N9) virus: a retrospective study in Eastern China, 2013–2014. Infect Dis Poverty. 2016;5(1):79. doi: 10.1186/s40249-016-0170-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 159.Sutton TC. The pandemic threat of emerging H5 and H7 avian influenza viruses. Viruses. 2018;10(9):E461. doi: 10.3390/v10090461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 160.Jernigan DB, Cox NJ. H7N9: preparing for the unexpected in influenza. Annu Rev Med. 2015;66(1):361–371. doi: 10.1146/annurev-med-010714-112311. [DOI] [PubMed] [Google Scholar]
  • 161.Silva W, Das TK, Izurieta R. Estimating disease burden of a potential A (H7N9) pandemic influenza outbreak in the United States. BMC Public Health. 2017;17(1):898. doi: 10.1186/s12889-017-4884-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 162.WHO. Human infection with avian influenza (H7N9) virus—China: update. 2018. https://www.who.int/csr/don/05-september-2018-ah7n9-china/en/ (accessed October 20, 2020)
  • 163.Su K, Ye S, Li Q, Xie W, Yu H, Qi L, Xiong Y, Zhao H, Li B, Ling H, Tang Y, Xiao B, Rong R, Tang W, Li Y. Influenza A (H7N9) virus emerged and resulted in human infections in Chongqing, southwestern China since 2017. Int J Infect Dis. 2019;81:244–250. doi: 10.1016/j.ijid.2019.02.011. [DOI] [PubMed] [Google Scholar]
  • 164.Yu D, Xiang G, Zhu W, Lei X, Li B, Meng Y, Yang L, Jiao H, Li X, Huang W, Wei H, Zhang Y, Hai Y, Zhang H, Yue H, Zou S, Zhao X, Li C, Ao D, Zhang Y, Tan M, Liu J, Zhang X, Gao GF, Meng L, Wang D. The re-emergence of highly pathogenic avian influenza H7N9 viruses in humans in mainland of China, 2019. Euro Surveill. 2019;24(21):1900273. doi: 10.2807/1560-7917.ES.2019.24.21.1900273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 165.Shi W, Ke C, Fang S, Li J, Song H, Li X, Hu T, Wu J, Chen T, Yi L, Song Y, Wang X, Xing W, Huang W, Xiao H, Liang L, Peng B, Wu W, Liu H, Liu WJ, Holmes EC, Gao GF, Wang D. Co-circulation and persistence of multiple A/H3N2 influenza variants in China. Emerg Microbes Infect. 2019;8(1):1157–1167. doi: 10.1080/22221751.2019.1648183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 166.Wang P, Liu WJ. It’s not just science: challenges for public health intervention in Ebola epidemics in the Democratic Republic of Congo. Sci China Life Sci. 2020;63(7):1079–1081. doi: 10.1007/s11427-019-1670-6. [DOI] [PubMed] [Google Scholar]
  • 167.Quan C, Wang Q, Zhang J, Zhao M, Dai Q, Huang T, Zhang Z, Mao S, Nie Y, Liu J, Xie Y, Zhang B, Bi Y, Shi W, Liu P, Wang D, Feng L, Yu H, Liu WJ, Gao GF. Avian influenza A viruses among occupationally exposed populations, China, 2014–2016. Emerg Infect Dis. 2019;25(12):2215–2225. doi: 10.3201/eid2512.190261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 168.OIE. Update on avian influenza in animals (types H5 and H7). https://www.oie.int/en/animal-health-in-the-world/update-on-avian-influenza/2018/ (accessed March 29, 2021)
  • 169.Bulach D, Halpin R, Spiro D, Pomeroy L, Janies D, Boyle DB. Molecular analysis of H7 avian influenza viruses from Australia and New Zealand: genetic diversity and relationships from 1976 to 2007. J Virol. 2010;84(19):9957–9966. doi: 10.1128/JVI.00930-10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 170.Huo X, Cui LB, Chen C, Wang D, Qi X, Zhou MH, Guo X, Wang F, Liu WJ, Kong W, Ni D, Chi Y, Ge Y, Huang H, Hu F, Li C, Zhao X, Ren R, Bao CJ, Gao GF, Zhu FC. Severe human infection with a novel avian-origin influenza A (H7N4) virus. Sci Bull (Beijing) 2018;63(16):1043–1050. doi: 10.1016/j.scib.2018.07.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 171.Quan C, Huang T, Chen X, Zhang J, Wang Q, Zhang C, Zhang T, Zhou L, Shu L, Long C, Yang L, Du X, Zhao Y, Liu P, Song H, Shi W, Bi Y, Lv Q, Liu WJ, Gao GF. Genomic characterizations of H4 subtype avian influenza viruses from live poultry markets in Sichuan Province of China, 2014–2015. Sci China Life Sci. 2018;61(9):1123–1126. doi: 10.1007/s11427-018-9327-4. [DOI] [PubMed] [Google Scholar]
  • 172.Gao GF. Foreword: Foreword from Editor-in-Chief George F. Gao — China’s outreach to the world: public health goes global. China CDC Week. 2019;1(1):1–2. doi: 10.46234/ccdcw2019.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 173.Wu G. Laboratory biosafety in China: past, present, and future. Biosafety Heal. 2019;1(2):56–58. doi: 10.1016/j.bsheal.2019.10.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 174.Liu Q, Zhou B, Ma W, Bawa B, Ma J, Wang W, Lang Y, Lyoo Y, Halpin RA, Lin X, Stockwell TB, Webby R, Wentworth DE, Richt JA. Analysis of recombinant H7N9 wild-type and mutant viruses in pigs shows that the Q226L mutation in HA is important for transmission. J Virol. 2014;88(14):8153–8165. doi: 10.1128/JVI.00894-14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 175.Mok CK, Lee HH, Chan MC, Sia SF, Lestra M, Nicholls JM, Zhu H, Guan Y, Peiris JM. Pathogenicity of the novel A/H7N9 influenza virus in mice. MBio. 2013;4(4):e00362–13. doi: 10.1128/mBio.00362-13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 176.Sun X, Belser JA, Yang H, Pulit-Penaloza JA, Pappas C, Brock N, Zeng H, Creager HM, Stevens J, Maines TR. Identification of key hemagglutinin residues responsible for cleavage, acid stability, and virulence of fifth-wave highly pathogenic avian influenza A (H7N9) viruses. Virology. 2019;535:232–240. doi: 10.1016/j.virol.2019.07.012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 177.Li W, Lee HHY, Li RF, Zhu HM, Yi G, Peiris JSM, Yang ZF, Mok CKP. The PB2 mutation with lysine at 627 enhances the pathogenicity of avian influenza (H7N9) virus which belongs to a non-zoonotic lineage. Sci Rep. 2017;7(1):2352. doi: 10.1038/s41598-017-02598-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 178.Liang L, Jiang L, Li J, Zhao Q, Wang J, He X, Huang S, Wang Q, Zhao Y, Wang G, Sun N, Deng G, Shi J, Tian G, Zeng X, Jiang Y, Liu L, Liu J, Chen P, Bu Z, Kawaoka Y, Chen H, Li C. Low polymerase activity attributed to PA drives the acquisition of the PB2 E627K mutation of H7N9 avian influenza virus in mammals. MBio. 2019;10(3):e01162–19. doi: 10.1128/mBio.01162-19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 179.Chan LL, Bui CT, Mok CK, Ng MM, Nicholls JM, Peiris JS, Chan MC, Chan RW. Evaluation of the human adaptation of influenza A/H7N9 virus in PB2 protein using human and swine respiratory tract explant cultures. Sci Rep. 2016;6(1):35401. doi: 10.1038/srep35401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 180.Zhu W, Zou X, Zhou J, Tang J, Shu Y. Residues 41V and/or 210D in the NP protein enhance polymerase activities and potential replication of novel influenza (H7N9) viruses at low temperature. Virol J. 2015;12(1):71. doi: 10.1186/s12985-015-0304-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 181.Ma S, Zhang B, Shi J, Yin X, Wang G, Cui P, Liu L, Deng G, Jiang Y, Li C, Chen H. Amino acid mutations A286V and T437M in the nucleoprotein attenuate H7N9 viruses in mice. J Virol. 2019;94(2):e01530–19. doi: 10.1128/JVI.01530-19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 182.Wang S, Zhang L, Zhang R, Chi X, Yang Z, Xie Y, Shu S, Liao Y, Chen JL. Identification of two residues within the NS1 of H7N9 influenza A virus that critically affect the protein stability and function. Vet Res (Faisalabad) 2018;49(1):98. doi: 10.1186/s13567-018-0594-y. [DOI] [PMC free article] [PubMed] [Google Scholar]

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