tetano
Editor, Senior Moderator
Cell Host Microbe
. 2026 Jan 14;34(1):103-115.e9.
doi: 10.1016/j.chom.2025.12.006.
Molecular basis of 60 years of antigenic evolution of human influenza A(H3N2) virus neuraminidase
Miruna E Rosu[SUP] 1 [/SUP], Kim B Westgeest[SUP] 1 [/SUP], Miranda de Graaf[SUP] 1 [/SUP], Blake M Hauser[SUP] 2 [/SUP], Sina Tureli[SUP] 2 [/SUP], Sarah James[SUP] 2 [/SUP], Felisita F Sinartio[SUP] 1 [/SUP], Theo M Bestebroer[SUP] 1 [/SUP], Pascal Lexmond[SUP] 1 [/SUP], Mark R Pronk[SUP] 1 [/SUP], Stefan van der Vliet[SUP] 1 [/SUP], Eugene Skepner[SUP] 2 [/SUP], Monique I J Spronken[SUP] 1 [/SUP], Barbara Mühlemann[SUP] 3 [/SUP], Mathilde Richard[SUP] 1 [/SUP], Terry C Jones[SUP] 3 [/SUP], Derek J Smith[SUP] 2 [/SUP], Sander Herfst[SUP] 1 [/SUP], Ron A M Fouchier[SUP] 4 [/SUP]
Affiliations
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.
Keywords: antigenic drift; evolution; influenza virus; neuraminidase; vaccines.
. 2026 Jan 14;34(1):103-115.e9.
doi: 10.1016/j.chom.2025.12.006.
Molecular basis of 60 years of antigenic evolution of human influenza A(H3N2) virus neuraminidase
Miruna E Rosu[SUP] 1 [/SUP], Kim B Westgeest[SUP] 1 [/SUP], Miranda de Graaf[SUP] 1 [/SUP], Blake M Hauser[SUP] 2 [/SUP], Sina Tureli[SUP] 2 [/SUP], Sarah James[SUP] 2 [/SUP], Felisita F Sinartio[SUP] 1 [/SUP], Theo M Bestebroer[SUP] 1 [/SUP], Pascal Lexmond[SUP] 1 [/SUP], Mark R Pronk[SUP] 1 [/SUP], Stefan van der Vliet[SUP] 1 [/SUP], Eugene Skepner[SUP] 2 [/SUP], Monique I J Spronken[SUP] 1 [/SUP], Barbara Mühlemann[SUP] 3 [/SUP], Mathilde Richard[SUP] 1 [/SUP], Terry C Jones[SUP] 3 [/SUP], Derek J Smith[SUP] 2 [/SUP], Sander Herfst[SUP] 1 [/SUP], Ron A M Fouchier[SUP] 4 [/SUP]
Affiliations
- PMID: 41539294
- DOI: 10.1016/j.chom.2025.12.006
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.
Keywords: antigenic drift; evolution; influenza virus; neuraminidase; vaccines.