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#Molecular basis of 60 years of #antigenic #evolution of #human #influenza #H3N2 virus neuraminidase

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By G.M.

 


Highlights

• Human influenza A virus N2 neuraminidases were analyzed by antigenic cartography

• N2 antigenic evolution was discordant with antigenic evolution of H3 hemagglutinin

• Important epitopes were identified at the NA active site but also elsewhere in NA

• Changes in charge, volume, and hydropathy of epitope residues caused antigenic drift


Summary

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.

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Link: https://www.cell.com/cell-host-microbe/abstract/S1931-3128(25)00525-6?rss=yes

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