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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
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.
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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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