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PLoS Pathog . The receptor binding properties of H5Ny influenza A viruses have evolved to bind to avian-type mucin-like O-glycans

tetano

Editor, Senior Moderator
PLoS Pathog


. 2026 Jan 20;22(1):e1013812.
doi: 10.1371/journal.ppat.1013812. Online ahead of print.
The receptor binding properties of H5Ny influenza A viruses have evolved to bind to avian-type mucin-like O-glycans

Julia Weber[SUP] 1 2 [/SUP], Niels L D Ponse[SUP] 1 [/SUP], Xueyong Zhu[SUP] 3 [/SUP], María Ríos Carrasco[SUP] 1 [/SUP], Alvin X Han[SUP] 4 [/SUP], Mathis Funk[SUP] 5 [/SUP], Ting-Hui Lin[SUP] 3 [/SUP], Alba Gabarroca García[SUP] 1 [/SUP], Cindy M Spruit[SUP] 1 [/SUP], Ding Zhang[SUP] 3 [/SUP], Wenli Yu[SUP] 3 [/SUP], Ian A Wilson[SUP] 3 6 [/SUP], Mathilde Richard[SUP] 5 [/SUP], Geert-Jan Boons[SUP] 1 7 [/SUP], Robert P de Vries[SUP] 1 [/SUP]


Affiliations
Abstract

Highly pathogenic H5Ny influenza A viruses are causing unprecedented, season-independent outbreaks across avian and mammalian species, including dairy cattle, a novel reservoir. The sialoside-binding properties of influenza A hemagglutinin (HA) are strongly related to its ability to infect and transmit between hosts. Mucin-like O-glycans, omnipresent in respiratory tracts, have been understudied as viral receptors due to their complexity. To address this, we synthesized 25 O-linked glycans with diverse sialosides, including modifications by fucosides and sulfates. Our findings reveal that H5Ny 2.3.4.4b viruses bind core 3 sialyl-Lewisx and Sia-Gal-β3GalNAc, O-linked glycans not recognized by classical H5 or other avian viruses. By determining crystal structures, we resolved the structural features of four glycans in an H5 hemagglutinin (HA) from a 2016 2.3.4.4b virus. While these viruses do not bind human-type receptors, their broad receptor specificity enhances binding to human tracheal tissues, suggesting that O-glycan recognition could contribute to the continues spillover of this clade.


 
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