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N-Glycolylneuraminic Acid Binding of Avian and Equine H7 Influenza A Viruses
Influenza A viruses (IAV) initiate infection by binding to glycans with terminal sialic acids on the cell surface. Hosts of IAV variably express two major forms of sialic acid, N-acetylneuraminic acid (NeuAc) and N-glycolylneuraminic acid (NeuGc). NeuGc is produced in most mammals, including horses...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906439/ https://www.ncbi.nlm.nih.gov/pubmed/35044215 http://dx.doi.org/10.1128/jvi.02120-21 |
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author | Spruit, Cindy M. Zhu, Xueyong Tomris, Ilhan Ríos-Carrasco, María Han, Alvin X. Broszeit, Frederik van der Woude, Roosmarijn Bouwman, Kim M. Luu, Michel M. T. Matsuno, Keita Sakoda, Yoshihiro Russell, Colin A. Wilson, Ian A. Boons, Geert-Jan de Vries, Robert P. |
author_facet | Spruit, Cindy M. Zhu, Xueyong Tomris, Ilhan Ríos-Carrasco, María Han, Alvin X. Broszeit, Frederik van der Woude, Roosmarijn Bouwman, Kim M. Luu, Michel M. T. Matsuno, Keita Sakoda, Yoshihiro Russell, Colin A. Wilson, Ian A. Boons, Geert-Jan de Vries, Robert P. |
author_sort | Spruit, Cindy M. |
collection | PubMed |
description | Influenza A viruses (IAV) initiate infection by binding to glycans with terminal sialic acids on the cell surface. Hosts of IAV variably express two major forms of sialic acid, N-acetylneuraminic acid (NeuAc) and N-glycolylneuraminic acid (NeuGc). NeuGc is produced in most mammals, including horses and pigs, but is absent in humans, ferrets, and birds. The only known naturally occurring IAV that exclusively bind NeuGc are extinct highly pathogenic equine H7N7 viruses. We determined the crystal structure of a representative equine H7 hemagglutinin (HA) in complex with NeuGc and observed high similarity in the receptor-binding domain with an avian H7 HA. To determine the molecular basis for NeuAc and NeuGc specificity, we performed systematic mutational analyses, based on the structural insights, on two distant avian H7 HAs and an H15 HA. We found that the A135E mutation is key for binding α2,3-linked NeuGc but does not abolish NeuAc binding. The additional mutations S128T, I130V, T189A, and K193R converted the specificity from NeuAc to NeuGc. We investigated the residues at positions 128, 130, 135, 189, and 193 in a phylogenetic analysis of avian and equine H7 HAs. This analysis revealed a clear distinction between equine and avian residues. The highest variability was observed at key position 135, of which only the equine glutamic acid led to NeuGc binding. These results demonstrate that genetically distinct H7 and H15 HAs can be switched from NeuAc to NeuGc binding and vice versa after the introduction of several mutations, providing insights into the adaptation of H7 viruses to NeuGc receptors. IMPORTANCE Influenza A viruses cause millions of cases of severe illness and deaths annually. To initiate infection and replicate, the virus first needs to bind to a structure on the cell surface, like a key fitting in a lock. For influenza A viruses, these “keys” (receptors) on the cell surface are chains of sugar molecules (glycans). The terminal sugar on these glycans is often either N-acetylneuraminic acid (NeuAc) or N-glycolylneuraminic acid (NeuGc). Most influenza A viruses bind NeuAc, but a small minority bind NeuGc. NeuGc is present in species like horses, pigs, and mice but not in humans, ferrets, and birds. Here, we investigated the molecular determinants of NeuGc specificity and the origin of viruses that bind NeuGc. |
format | Online Article Text |
id | pubmed-8906439 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-89064392022-03-10 N-Glycolylneuraminic Acid Binding of Avian and Equine H7 Influenza A Viruses Spruit, Cindy M. Zhu, Xueyong Tomris, Ilhan Ríos-Carrasco, María Han, Alvin X. Broszeit, Frederik van der Woude, Roosmarijn Bouwman, Kim M. Luu, Michel M. T. Matsuno, Keita Sakoda, Yoshihiro Russell, Colin A. Wilson, Ian A. Boons, Geert-Jan de Vries, Robert P. J Virol Virus-Cell Interactions Influenza A viruses (IAV) initiate infection by binding to glycans with terminal sialic acids on the cell surface. Hosts of IAV variably express two major forms of sialic acid, N-acetylneuraminic acid (NeuAc) and N-glycolylneuraminic acid (NeuGc). NeuGc is produced in most mammals, including horses and pigs, but is absent in humans, ferrets, and birds. The only known naturally occurring IAV that exclusively bind NeuGc are extinct highly pathogenic equine H7N7 viruses. We determined the crystal structure of a representative equine H7 hemagglutinin (HA) in complex with NeuGc and observed high similarity in the receptor-binding domain with an avian H7 HA. To determine the molecular basis for NeuAc and NeuGc specificity, we performed systematic mutational analyses, based on the structural insights, on two distant avian H7 HAs and an H15 HA. We found that the A135E mutation is key for binding α2,3-linked NeuGc but does not abolish NeuAc binding. The additional mutations S128T, I130V, T189A, and K193R converted the specificity from NeuAc to NeuGc. We investigated the residues at positions 128, 130, 135, 189, and 193 in a phylogenetic analysis of avian and equine H7 HAs. This analysis revealed a clear distinction between equine and avian residues. The highest variability was observed at key position 135, of which only the equine glutamic acid led to NeuGc binding. These results demonstrate that genetically distinct H7 and H15 HAs can be switched from NeuAc to NeuGc binding and vice versa after the introduction of several mutations, providing insights into the adaptation of H7 viruses to NeuGc receptors. IMPORTANCE Influenza A viruses cause millions of cases of severe illness and deaths annually. To initiate infection and replicate, the virus first needs to bind to a structure on the cell surface, like a key fitting in a lock. For influenza A viruses, these “keys” (receptors) on the cell surface are chains of sugar molecules (glycans). The terminal sugar on these glycans is often either N-acetylneuraminic acid (NeuAc) or N-glycolylneuraminic acid (NeuGc). Most influenza A viruses bind NeuAc, but a small minority bind NeuGc. NeuGc is present in species like horses, pigs, and mice but not in humans, ferrets, and birds. Here, we investigated the molecular determinants of NeuGc specificity and the origin of viruses that bind NeuGc. American Society for Microbiology 2022-03-09 /pmc/articles/PMC8906439/ /pubmed/35044215 http://dx.doi.org/10.1128/jvi.02120-21 Text en Copyright © 2022 Spruit 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 | Virus-Cell Interactions Spruit, Cindy M. Zhu, Xueyong Tomris, Ilhan Ríos-Carrasco, María Han, Alvin X. Broszeit, Frederik van der Woude, Roosmarijn Bouwman, Kim M. Luu, Michel M. T. Matsuno, Keita Sakoda, Yoshihiro Russell, Colin A. Wilson, Ian A. Boons, Geert-Jan de Vries, Robert P. N-Glycolylneuraminic Acid Binding of Avian and Equine H7 Influenza A Viruses |
title | N-Glycolylneuraminic Acid Binding of Avian and Equine H7 Influenza A Viruses |
title_full | N-Glycolylneuraminic Acid Binding of Avian and Equine H7 Influenza A Viruses |
title_fullStr | N-Glycolylneuraminic Acid Binding of Avian and Equine H7 Influenza A Viruses |
title_full_unstemmed | N-Glycolylneuraminic Acid Binding of Avian and Equine H7 Influenza A Viruses |
title_short | N-Glycolylneuraminic Acid Binding of Avian and Equine H7 Influenza A Viruses |
title_sort | n-glycolylneuraminic acid binding of avian and equine h7 influenza a viruses |
topic | Virus-Cell Interactions |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906439/ https://www.ncbi.nlm.nih.gov/pubmed/35044215 http://dx.doi.org/10.1128/jvi.02120-21 |
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