9NRR

Crystal structure of the H5 influenza virus hemagglutinin from A/duck/France/161108h/2016 (H5N8) clade 2.3.4.4b

Summary for 9NRR

• Entry DOI: 10.2210/pdb9nrr/pdb
• Descriptor: Hemagglutinin HA1 chain, 1,2-ETHANEDIOL, SULFATE ION, ... (14 entities in total)
• Functional Keywords: h5 hemagglutinin, clade 2.3.4.4b, o-linked glycan, receptor specificity, viral protein
• Biological source: Influenza A virus; More
• Total number of polymer chains: 6
• Total formula weight: 183925.24

Authors

Zhu, X.,Wilson, I.A. (deposition date: 2025-03-14, release date: 2026-01-14, Last modification date: 2026-01-28)

Primary citation

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.
The receptor binding properties of H5Ny influenza A viruses have evolved to bind to avian-type mucin-like O-glycans.
Plos Pathog., 22:e1013812-e1013812, 2026

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.

PubMed: 41557749
DOI: 10.1371/journal.ppat.1013812

Experimental method

X-RAY DIFFRACTION (1.94 Å)