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Plasticity of the Influenza Virus H5 HA Protein

Since the emergence of highly pathogenic avian influenza viruses of the H5 subtype, the major viral antigen, hemagglutinin (HA), has undergone constant evolution, resulting in numerous genetic and antigenic (sub)clades. To explore the consequences of amino acid changes at sites that may affect the a...

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Autores principales: Kong, Huihui, Burke, David F., da Silva Lopes, Tiago Jose, Takada, Kosuke, Imai, Masaki, Zhong, Gongxun, Hatta, Masato, Fan, Shufang, Chiba, Shiho, Smith, Derek, Neumann, Gabriele, Kawaoka, Yoshihiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885105/
https://www.ncbi.nlm.nih.gov/pubmed/33563825
http://dx.doi.org/10.1128/mBio.03324-20
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author Kong, Huihui
Burke, David F.
da Silva Lopes, Tiago Jose
Takada, Kosuke
Imai, Masaki
Zhong, Gongxun
Hatta, Masato
Fan, Shufang
Chiba, Shiho
Smith, Derek
Neumann, Gabriele
Kawaoka, Yoshihiro
author_facet Kong, Huihui
Burke, David F.
da Silva Lopes, Tiago Jose
Takada, Kosuke
Imai, Masaki
Zhong, Gongxun
Hatta, Masato
Fan, Shufang
Chiba, Shiho
Smith, Derek
Neumann, Gabriele
Kawaoka, Yoshihiro
author_sort Kong, Huihui
collection PubMed
description Since the emergence of highly pathogenic avian influenza viruses of the H5 subtype, the major viral antigen, hemagglutinin (HA), has undergone constant evolution, resulting in numerous genetic and antigenic (sub)clades. To explore the consequences of amino acid changes at sites that may affect the antigenicity of H5 viruses, we simultaneously mutated 17 amino acid positions of an H5 HA by using a synthetic gene library that, theoretically, encodes all combinations of the 20 amino acids at the 17 positions. All 251 mutant viruses sequenced possessed ≥13 amino acid substitutions in HA, demonstrating that the targeted sites can accommodate a substantial number of mutations. Selection with ferret sera raised against H5 viruses of different clades resulted in the isolation of 39 genotypes. Further analysis of seven variants demonstrated that they were antigenically different from the parental virus and replicated efficiently in mammalian cells. Our data demonstrate the substantial plasticity of the influenza virus H5 HA protein, which may lead to novel antigenic variants.
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spelling pubmed-78851052021-02-19 Plasticity of the Influenza Virus H5 HA Protein Kong, Huihui Burke, David F. da Silva Lopes, Tiago Jose Takada, Kosuke Imai, Masaki Zhong, Gongxun Hatta, Masato Fan, Shufang Chiba, Shiho Smith, Derek Neumann, Gabriele Kawaoka, Yoshihiro mBio Research Article Since the emergence of highly pathogenic avian influenza viruses of the H5 subtype, the major viral antigen, hemagglutinin (HA), has undergone constant evolution, resulting in numerous genetic and antigenic (sub)clades. To explore the consequences of amino acid changes at sites that may affect the antigenicity of H5 viruses, we simultaneously mutated 17 amino acid positions of an H5 HA by using a synthetic gene library that, theoretically, encodes all combinations of the 20 amino acids at the 17 positions. All 251 mutant viruses sequenced possessed ≥13 amino acid substitutions in HA, demonstrating that the targeted sites can accommodate a substantial number of mutations. Selection with ferret sera raised against H5 viruses of different clades resulted in the isolation of 39 genotypes. Further analysis of seven variants demonstrated that they were antigenically different from the parental virus and replicated efficiently in mammalian cells. Our data demonstrate the substantial plasticity of the influenza virus H5 HA protein, which may lead to novel antigenic variants. American Society for Microbiology 2021-02-09 /pmc/articles/PMC7885105/ /pubmed/33563825 http://dx.doi.org/10.1128/mBio.03324-20 Text en Copyright © 2021 Kong et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Kong, Huihui
Burke, David F.
da Silva Lopes, Tiago Jose
Takada, Kosuke
Imai, Masaki
Zhong, Gongxun
Hatta, Masato
Fan, Shufang
Chiba, Shiho
Smith, Derek
Neumann, Gabriele
Kawaoka, Yoshihiro
Plasticity of the Influenza Virus H5 HA Protein
title Plasticity of the Influenza Virus H5 HA Protein
title_full Plasticity of the Influenza Virus H5 HA Protein
title_fullStr Plasticity of the Influenza Virus H5 HA Protein
title_full_unstemmed Plasticity of the Influenza Virus H5 HA Protein
title_short Plasticity of the Influenza Virus H5 HA Protein
title_sort plasticity of the influenza virus h5 ha protein
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885105/
https://www.ncbi.nlm.nih.gov/pubmed/33563825
http://dx.doi.org/10.1128/mBio.03324-20
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