Download MendeleyThe receptor binding properties of H5Ny influenza A viruses have evolved to bind to avian-type mucin-like O-glycans.
Weber, J., Ponse, N.L.D., Zhu, X., Carrasco, M.R., Han, A.X., Funk, M., Lin, T.H., Garcia, A.G., Spruit, C.M., Zhang, D., Yu, W., Wilson, I.A., Richard, M., Boons, G.J., de Vries, R.P.(2026) PLoS Pathog 22: e1013812-e1013812
- PubMed: 41557749
- DOI: https://doi.org/10.1371/journal.ppat.1013812
- Primary Citation of Related Structures:
9NRR, 9NRS, 9NRT, 9NRU, 9NRV - PubMed 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.
- Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg Utrecht, Utrecht, The Netherlands.
Organizational Affiliation:
