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N-linked glycosylation enhances hemagglutinin stability in avian H5N6 influenza virus to promote adaptation in mammals
Clade 2.3.4.4 avian H5Ny viruses, namely H5N2, H5N6, and H5N8, have exhibited unprecedented intercontinental spread in poultry. Among them, only H5N6 viruses are frequently reported to infect mammals and cause serious human infections. In this study, the genetic and biological characteristics of sur...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9896958/ https://www.ncbi.nlm.nih.gov/pubmed/36741455 http://dx.doi.org/10.1093/pnasnexus/pgac085 |
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author | Sun, Honglei Deng, Guojing Sun, Haoran Song, Jingwei Zhang, Wei Li, Han Wei, Xiaohui Li, Fangtao Zhang, Xin Liu, Jiyu Pu, Juan Sun, Yipeng Tong, Qi Bi, Yuhai Xie, Yufeng Qi, Jianxun Chang, Kin-Chow Gao, George Fu Liu, Jinhua |
author_facet | Sun, Honglei Deng, Guojing Sun, Haoran Song, Jingwei Zhang, Wei Li, Han Wei, Xiaohui Li, Fangtao Zhang, Xin Liu, Jiyu Pu, Juan Sun, Yipeng Tong, Qi Bi, Yuhai Xie, Yufeng Qi, Jianxun Chang, Kin-Chow Gao, George Fu Liu, Jinhua |
author_sort | Sun, Honglei |
collection | PubMed |
description | Clade 2.3.4.4 avian H5Ny viruses, namely H5N2, H5N6, and H5N8, have exhibited unprecedented intercontinental spread in poultry. Among them, only H5N6 viruses are frequently reported to infect mammals and cause serious human infections. In this study, the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) were examined for adaptation in mammalian infection. Phylogenetic analysis identified an amino acid (AA) deletion at position 131 of HA as a distinctive feature of H5N6 virus isolated from human patients. This single AA deletion was found to enhance H5N6 virus replication and pathogenicity in vitro and in mammalian hosts (mice and ferrets) through HA protein acid and thermal stabilization that resulted in reduced pH threshold from pH 5.7 to 5.5 for viral-endosomal membrane fusion. Mass spectrometry and crystal structure revealed that the AA deletion in HA at position 131 introduced an N-linked glycosylation site at 129, which increases compactness between HA monomers, thus stabilizes the trimeric structure. Our findings provide a molecular understanding of how HA protein stabilization promotes cross-species avian H5N6 virus infection to mammalian hosts. |
format | Online Article Text |
id | pubmed-9896958 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-98969582023-02-04 N-linked glycosylation enhances hemagglutinin stability in avian H5N6 influenza virus to promote adaptation in mammals Sun, Honglei Deng, Guojing Sun, Haoran Song, Jingwei Zhang, Wei Li, Han Wei, Xiaohui Li, Fangtao Zhang, Xin Liu, Jiyu Pu, Juan Sun, Yipeng Tong, Qi Bi, Yuhai Xie, Yufeng Qi, Jianxun Chang, Kin-Chow Gao, George Fu Liu, Jinhua PNAS Nexus Biological, Health, and Medical Sciences Clade 2.3.4.4 avian H5Ny viruses, namely H5N2, H5N6, and H5N8, have exhibited unprecedented intercontinental spread in poultry. Among them, only H5N6 viruses are frequently reported to infect mammals and cause serious human infections. In this study, the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) were examined for adaptation in mammalian infection. Phylogenetic analysis identified an amino acid (AA) deletion at position 131 of HA as a distinctive feature of H5N6 virus isolated from human patients. This single AA deletion was found to enhance H5N6 virus replication and pathogenicity in vitro and in mammalian hosts (mice and ferrets) through HA protein acid and thermal stabilization that resulted in reduced pH threshold from pH 5.7 to 5.5 for viral-endosomal membrane fusion. Mass spectrometry and crystal structure revealed that the AA deletion in HA at position 131 introduced an N-linked glycosylation site at 129, which increases compactness between HA monomers, thus stabilizes the trimeric structure. Our findings provide a molecular understanding of how HA protein stabilization promotes cross-species avian H5N6 virus infection to mammalian hosts. Oxford University Press 2022-06-08 /pmc/articles/PMC9896958/ /pubmed/36741455 http://dx.doi.org/10.1093/pnasnexus/pgac085 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of National Academy of Sciences. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Biological, Health, and Medical Sciences Sun, Honglei Deng, Guojing Sun, Haoran Song, Jingwei Zhang, Wei Li, Han Wei, Xiaohui Li, Fangtao Zhang, Xin Liu, Jiyu Pu, Juan Sun, Yipeng Tong, Qi Bi, Yuhai Xie, Yufeng Qi, Jianxun Chang, Kin-Chow Gao, George Fu Liu, Jinhua N-linked glycosylation enhances hemagglutinin stability in avian H5N6 influenza virus to promote adaptation in mammals |
title | N-linked glycosylation enhances hemagglutinin stability in avian H5N6 influenza virus to promote adaptation in mammals |
title_full | N-linked glycosylation enhances hemagglutinin stability in avian H5N6 influenza virus to promote adaptation in mammals |
title_fullStr | N-linked glycosylation enhances hemagglutinin stability in avian H5N6 influenza virus to promote adaptation in mammals |
title_full_unstemmed | N-linked glycosylation enhances hemagglutinin stability in avian H5N6 influenza virus to promote adaptation in mammals |
title_short | N-linked glycosylation enhances hemagglutinin stability in avian H5N6 influenza virus to promote adaptation in mammals |
title_sort | n-linked glycosylation enhances hemagglutinin stability in avian h5n6 influenza virus to promote adaptation in mammals |
topic | Biological, Health, and Medical Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9896958/ https://www.ncbi.nlm.nih.gov/pubmed/36741455 http://dx.doi.org/10.1093/pnasnexus/pgac085 |
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