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Avian-to-Human Receptor-Binding Adaptation of Avian H7N9 Influenza Virus Hemagglutinin

tetano

Editor, Senior Moderator
Cell Rep. 2019 Nov 19;29(8):2217-2228.e5. doi: 10.1016/j.celrep.2019.10.047. [h=1]Avian-to-Human Receptor-Binding Adaptation of Avian H7N9 Influenza Virus Hemagglutinin.[/h]
Xu Y[SUP]1[/SUP], Peng R[SUP]2[/SUP], Zhang W[SUP]2[/SUP], Qi J[SUP]2[/SUP], Song H[SUP]3[/SUP], Liu S[SUP]1[/SUP], Wang H[SUP]4[/SUP], Wang M[SUP]2[/SUP], Xiao H[SUP]5[/SUP], Fu L[SUP]6[/SUP], Fan Z[SUP]2[/SUP], Bi Y[SUP]6[/SUP], Yan J[SUP]7[/SUP], Shi Y[SUP]8[/SUP], Gao GF[SUP]9[/SUP].
[h=3]Author information[/h] 1 School of Life Sciences, University of Science and Technology of China, Hefei 230026, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China. 2 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China. 3 Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China. 4 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China; Laboratory of Animal Infectious Diseases, College of Animal Sciences and Veterinary Medicine, Guangxi University, Nanning 530004, China. 5 Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China. 6 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China; Center for Influenza Research and Early-Warning, Chinese Academy of Sciences (CASCIRE), Beijing 100101, China. 7 Center for Influenza Research and Early-Warning, Chinese Academy of Sciences (CASCIRE), Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China; Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China. 8 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China; Center for Influenza Research and Early-Warning, Chinese Academy of Sciences (CASCIRE), Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China; Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China. 9 School of Life Sciences, University of Science and Technology of China, Hefei 230026, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China; Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China; Laboratory of Animal Infectious Diseases, College of Animal Sciences and Veterinary Medicine, Guangxi University, Nanning 530004, China; Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China; Center for Influenza Research and Early-Warning, Chinese Academy of Sciences (CASCIRE), Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China; Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China. Electronic address: gaof@im.ac.cn.

[h=3]Abstract[/h] Since 2013, H7N9 avian influenza viruses (AIVs) have caused more than 1,600 human infections, posing a threat to public health. An emerging concern is whether H7N9 AIVs will cause pandemics among humans. Molecular analysis of hemagglutinin (HA), which is a critical determinant of interspecies transmission, shows that the current H7N9 AIVs are still dual-receptor tropic, indicating limited human-to-human transmission potency. Mutagenesis and structural studies reveal that a G186V substitution is sufficient for H7N9 AIVs to acquire human receptor-binding capacity, and a Q226L substitution would favor binding to both avian and human receptors only when paired with A138/V186/P221 hydrophobic residues. These data suggest a different evolutionary route of H7N9 viruses compared to other AIV-subtype HAs.
Copyright ? 2019 The Authors. Published by Elsevier Inc. All rights reserved.


[h=4]KEYWORDS:[/h] H7N9; hemagglutinin; influenza A virus; interspecies transmission; receptor-binding property; structural basis

PMID: 31747596 DOI: 10.1016/j.celrep.2019.10.047
 
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