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

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By G.M.

 


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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Link: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1013812

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