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Host Switching Mutations in H5N1 Influenza Hemagglutinin Suppress Site-specific Activation Dynamics.


ABSTRACT: Increase in the occurrence of human H5N1 spillover infections resulting from dissemination of highly pathogenic avian influenza (HPAI) virus into bird and mammal populations raises concerns about HPAI adapting to become human transmissible. Studies identified hemagglutinin (HA) acid stability and receptor preference as essential traits that shape host tropism. Mutations that increase HA stability and affinity for α-2,6-linked sialic acids have been shown to confer airborne transmissibility in a ferret model, however mechanisms of activation of H5 subtype HA have not been probed and the effect of adaptive mutations on HA function has been largely inferred from static structures. Here, we use hydrogen/deuterium-exchange mass spectrometry to dissect activation dynamics for two ancestral HPAI

SUBMITTER: Kephart SM 

PROVIDER: S-EPMC12632395 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature