Summary
A bioRxiv preprint comparing human H1N1 strains collected from 1977 to 2024 reports a recurring preference for α2,6-sialylated glycans. The study also found changes in binding avidity and a binding-null egg-adapted mutant.
A bioRxiv preprint reports that human H1N1 influenza strains collected between 1977 and 2024 repeatedly preferred binding to α2,6-sialylated di-LacNAc N-glycans. The researchers examined glycan binding with ELISA, flow cytometry and tissue histochemistry, tracing how this property varied as the virus evolved. The study is a preprint and has not yet been peer reviewed.
Hemagglutinin (HA), a protein on the influenza virus surface, binds sugars on cell surfaces as part of the process by which the virus attaches to cells. Sialic acids can connect to neighbouring sugars in different ways, including α2,6 and α2,3 linkages. Di-LacNAc N-glycans are sugar-chain structures containing two N-acetyllactosamine units. The arrangement of these sugars provides a way to compare receptor-binding preferences between viruses.
A recurring preference across decades
Across the strains examined, the researchers found a repeated preference for α2,6-sialylated di-LacNAc glycans. Binding to α2,3-sialylated glycans was generally undetectable in their tests. Two strains—A/Hongkong/117/1977 and A/New Caledonia/20/1999—also bound chicken tracheal tissue, a result reported from the tissue-histochemistry work.
The study links variation in binding to amino-acid substitutions in and around HA’s receptor-binding site. These substitutions have accumulated during H1N1 evolution, largely under antigenic pressure, according to the authors. Post-pandemic H1N1 viruses varied in their relative binding avidities, and the effects of the relevant amino acids differed when examined in pre-pandemic HA proteins. The authors also report a classical egg-adapted H1N1 mutant with no detectable binding across the assay platforms.
A further comparison in the abstract is with H3N2: the examined H1N1 viruses retained binding to glycans associated with avian erythrocyte haemagglutination, a pattern the authors say differs from H3N2 viruses.
What glycan binding can tell us
The results provide a long-term view of one part of influenza biology: how HA recognises particular sugar structures. That matters because receptor binding is involved in viral attachment, while changes in HA can alter the interaction. The findings point to both a recurring preference across the sampled H1N1 viruses and variation in how strongly they bound.
These experiments characterize binding in laboratory and tissue assays. Viral infection and spread also involve other biological steps, so the findings are best understood as evidence about receptor recognition rather than a direct measure of disease severity or transmission.