• Abdelwhab EM, Veits J, Ulrich R, Kasbohm E, Teifke JP, Mettenleiter TC. Composition of the Hemagglutinin Polybasic Proteolytic Cleavage Motif Mediates Variable Virulence of H7N7 Avian Influenza Viruses. Sci Rep. 2016;6:39505.

  • 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;8:94-102.

  • Bullough PA, Hughson FM, Skehel JJ, Wiley DC. Structure of influenza haemagglutinin at the pH of membrane fusion. Nature 1994;371:37-43.

  • Carr CM, Chaudhry C, Kim PS. Influenza hemagglutinin is spring-loaded by a metastable native conformation. Proc Natl Acad Sci U S A. 1997;94:14306-14313.

  • Cotter CR, Jin H, Chen Z. A single amino acid in the stalk region of the H1N1pdm influenza virus HA protein affects viral fusion, stability and infectivity. PLoS Pathog. 2014;10:e1003831.

  • Hoffmann E, Neumann G, Kawaoka Y, Hobom G, and Webster RG. A DNA transfection system for generation of influenza A virus from eight plasmids. Proc Natl Acad Sci U S A. 2000;97:6108-6113.

  • Horimoto T, Kawaoka Y. Biologic effects of introducing additional basic amino acid residues into the hemagglutinin cleavage site of a virulent avian influenza virus. Virus Res. 1997;50:35-40.

  • 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;22:615-626.

  • Ito T, Goto H, Yamamoto E, Tanaka H, Takeuchi M, Kuwayama M, Kawaoka Y, Otsuki K. Generation of a highly pathogenic avian influenza A virus from an avirulent field isolate by passaging in chickens. J Virol. 2001;75:4439-4443.

  • Jiang H, Wu P, Uyeki TM, He J, Deng Z, Xu W, Lv Q, Zhang J, Wu Y, Tsang TK, Kang M, Zheng J, Wang L, Yang B, Qin Y, Feng L, Fang VJ, Gao GF, Leung GM, Yu H, Cowling BJ. Preliminary Epidemiologic Assessment of Human Infections With Highly Pathogenic Avian Influenza A(H5N6) Virus, China. Clin Infect Dis. 2017;65:383-388.

  • Khatchikian D, Orlich M, Rott R. Increased viral pathogenicity after insertion of a 28S ribosomal RNA sequence into the haemagglutinin gene of an influenza virus. Nature. 1989;340:156-157.

  • Lee CW, Lee YJ, Senne DA, Suarez DL. Pathogenic potential of North American H7N2 avian influenza virus: a mutagenesis study using reverse genetics. Virology. 2006;353:388-395.

  • 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;381:1926-1932.

  • Liu D, Zhang Z, He L, Gao Z, Li J, Gu M, Hu J, Wang X, Liu X, Liu X. Characteristics of the emerging chicken-origin highly pathogenic H7N9 viruses: A new threat to public health and poultry industry. J Infect. 2018;76:217-220.

  • Orlich M, Gottwald H, Rott R. Nonhomologous recombination between the hemagglutinin gene and the nucleoprotein gene of an influenza virus. Virology. 1994;204:462-465.

  • 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:e00921-17.

  • 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:e00301-e00318.

  • Rott R. The pathogenic determinant of influenza virus. Vet Microbiol. 1992;33:303-310.

  • Russell CJ, Hu M, Okda FA. Influenza Hemagglutinin Protein Stability, Activation, and Pandemic Risk. Trends Microbiol. 2018;26:841-853.

  • Scholtissek C. Stability of infectious influenza A viruses at low pH and at elevated temperature. Vaccine. 1985;3:215 -218.

  • Seekings AH, Howard WA, Nunez A, Slomka MJ, Banyard AC, Hicks D, Ellis RJ, Nunez-Garcia J, Hartgroves LC, Barclay WS, Banks J, Brown IH. The Emergence of H7N7 Highly Pathogenic Avian Influenza Virus from Low Pathogenicity Avian Influenza Virus Using an in ovo Embryo Culture Model. Viruses. 2020;12:920.

  • 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;27:1409-1421.

  • Shi J, Deng G, Ma S, Zeng X, Yin X, Li M, Zhang B, Cui P, Chen Y, Yang H, Wan X, Liu L, Chen P, Jiang Y, Guan Y, Liu J, Gu W, Han S, Song Y, Liang L, Qu Z, Hou Y, Wang X, Bao H, Tian G, Li Y, Jiang L, Li C, Chen H. Rapid Evolution of H7N9 Highly Pathogenic Viruses that Emerged in China in 2017. Cell Host Microbe. 2018;24:558-568.

  • Suarez DL, Senne DA, Banks J, Brown IH, Essen SC, Lee CW, Manvell RJ, Mathieu-Benson C, Moreno V, Pedersen JC, Panigrahy B, Rojas H, Spackman E, Alexander DJ. Recombination resulting in virulence shift in avian influenza outbreak, Chile. Emerg Infect Dis. 2004;10:693-699.

  • 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.

  • 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 China, 2013-17: an epidemiological study of laboratory-confirmed case series. Lancet Infect Dis. 2017;17:822-832.

  • Webster RG, Rott R. Influenza virus A pathogenicity: the pivotal role of hemagglutinin. Cell. 1987;50:665-666.

  • Yang W, Yin X, Guan L, Li M, Ma S, Shi J, Deng G, Suzuki Y, Chen H. A live attenuated vaccine prevents replication and transmission of H7N9 highly pathogenic influenza viruses in mammals. Emerg Microbes Infect. 2018;7:153.

  • 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;75:71-75.

  • Zhang J, Ye H, Li H, Ma K, Qiu W, Chen Y, Qiu Z, Li B, Jia W, Liang Z, Liao M, Qi W. Evolution and Antigenic Drift of Influenza A (H7N9) Viruses, China, 2017-2019. Emerg Infect Dis. 2020;26:1906 -1911.

  • Zhang Y, Sun Y, Sun H, Pu J, Bi Y, Shi Y, Lu X, Li J, Zhu Q, Gao GF, Yang H, Liu J. A single amino acid at the hemagglutinin cleavage site contributes to the pathogenicity and neurovirulence of H5N1 influenza virus in mice. J Virol. 2012;86:6924-6931.

  • Zhu W, Dong J, Zhang Y, Yang L, Li X, Chen T, Zhao X, Wei H, Bo H, Zeng X, Huang W, Li Z, Tang J, Zhou J, Gao R, Xin L, Yang J, Zou S, Chen W, Liu J, Shu Y, Wang D. A Gene Constellation in Avian Influenza A (H7N9) Viruses May Have Facilitated the Fifth Wave Outbreak in China. Cell Rep. 2018;23:909 -917