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Molecular basis of 60 years of antigenic evolution of human influenza A(H3N2) virus neuraminidase.

Title: Molecular basis of 60 years of antigenic evolution of human influenza A(H3N2) virus neuraminidase.
Authors: Rosu, Miruna E; Westgeest, Kim B; de Graaf, Miranda; Hauser, Blake M; Tureli, Sina; James, Sarah; Sinartio, Felisita F; Bestebroer, Theo M; Lexmond, Pascal; Pronk, Mark R; van der Vliet, Stefan; Skepner, Eugene; Spronken, Monique IJ; Mühlemann, Barbara; Richard, Mathilde; Jones, Terry C; Smith, Derek J; Herfst, Sander; Fouchier, Ron AM
Publisher Information: Elsevier; Department of Zoology; //doi.org/10.1016/j.chom.2025.12.006
Publication Year: 2026
Collection: Apollo - University of Cambridge Repository
Subject Terms: antigenic drift; evolution; influenza virus; neuraminidase; vaccines; Influenza A Virus; H3N2 Subtype; Humans; Antigens; Viral; Molecular; Influenza; Human; Hemagglutinin Glycoproteins; H2N2 Subtype; Viral Proteins
Description: Human influenza A viruses escape antibody-mediated immunity through changes in the hemagglutinin (HA) and neuraminidase (NA) glycoproteins. HA antigenic evolution has been studied extensively, with more recent interest in NA due to its importance in influenza vaccine efficacy. Here, the antigenic properties of the NA of more than 300 A(H3N2) and A(H2N2) viruses isolated since 1957 were quantified with a NA inhibition enzyme-linked lectin assay and visualized using antigenic cartography, with follow-up molecular studies using recombinant viruses. The antigenic evolution of N2 NA was more gradual than that described for H3 HA, and antigenic changes in NA and HA were discordant. Multiple substitutions around the NA active site and tetramer lateral side that alter the charge, volume, or hydropathy of amino acids collectively determined antigenic properties. These data facilitate sequence-based genomic surveillance and inference of antigenic phenotypes from genotypes and offer opportunities to improve influenza vaccine effectiveness through increased focus on NA.
Document Type: article in journal/newspaper
File Description: Print; application/pdf
Language: English
Relation: https://www.repository.cam.ac.uk/handle/1810/399546; https://doi.org/10.17863/CAM.128048
DOI: 10.17863/CAM.128048
Availability: https://www.repository.cam.ac.uk/handle/1810/399546; https://doi.org/10.17863/CAM.128048
Rights: Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.20E53648
Database: BASE