Abstract
The global outbreak of highly pathogenic avian influenza (HPAI) A(H5N1) among birds and the spillover to mammals increases the risk for humans. A recent case in British Columbia with a clade 2.3.4.4b H5 virus infection revealed a mixture of 226Q/H in the receptor-binding site of hemagglutinin. While significant changes in pre-existing immunity by H1 or H3 polyclonal sera are not evident, we show that the Q226H mutation enables binding to human-type α2-6 sialic acid receptors. High-resolution cryo-EM structures provide a basis for the alteration in receptor preference and show that a possible path towards human adaptation also requires a conformational change of the bound α2-6-sialylated glycan. Continued surveillance for additional mutations that could enhance this phenotype is warranted.
Competing Interest Statement
The authors have declared no competing interest.
Funder Information Declared
Ministry of Technology and Innovation through Striving for Pandemic Preparedness—The Alberta Research Consortium
Canada Excellence Research Chair Program
Alberta Innovates Graduate Student Scholarship
Canada Biomedical Research Fund grant
Biosciences Research Infrastructure Fund grant
Natural Sciences and Engineering Research Council of Canada Discovery Grant
Natural Sciences and Engineering Research Council of Canada
Canada Foundation for Innovation
Alberta Innovation and Advanced Education Research Capacity Program
Source:
Link: https://www.biorxiv.org/content/10.64898/2026.05.21.726965v1
____
No comments:
Post a Comment