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Loss of α2,3-linked #sialoside in the receptor-binding site of a #H5N1 #influenza hemagglutinin identified in a #human patient

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By G.M.

 


Abstract

In November 2024, an adolescent female in British Columbia was hospitalized presenting with severe symptoms including respiratory failure due to infection with a novel H5N1 subtype influenza strain (BC24). Using cryogenic electron microscopy (cryo-EM), we show here that the N169 α2,3-linked auto-glycan that is found in the sialic acid binding site of previously studied H5 hemagglutinin (HA) proteins is absent in purified BC24 HA protein, suggesting greatly reduced affinity for α2,3-linked sialosides. Glycan microarray analysis shows that the BC24 HA protein displays reduced or no binding not just to most α2,3-linked sialosides, but also to α2,6-linked sialosides. Full-length BC24 HA expressed in A549 lung alveolar carcinoma cells drives membrane fusion, albeit at significantly lower levels than previous H5 HA proteins, and post-infection sera from the patient display strong binding to BC24 HA and HA proteins from other influenza subtypes. The high virulence of the BC24 strain despite weak receptor binding reveals further complexity in the factors that result in severe disease caused by avian influenza.


Competing Interest Statement

The authors have declared no competing interest.


Funder Information Declared

Canada Biomedical Research Fund

Canada Excellence Research Chairs, https://ror.org/02tvrwm90

Source: 


Link: https://www.biorxiv.org/content/10.64898/2026.01.19.700419v1

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