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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
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.
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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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