Five decades of human H1N1 evolution reveal conserved glycan receptor specificity

Over the past five decades, human H1N1 influenza viruses have continuously circulated among populations, undergoing constant evolution. This evolution has led to changes in the hemagglutinin protein, particularly in and around the receptor-binding site (RBS), as a result of antigenic pressure which can alter the way these viruses recognize and bind to receptors.

To explore the glycan-binding properties of these viruses, researchers examined H1N1 strains collected between 1977 and 2024 using techniques such as ELISA, flow cytometry, and tissue histochemistry. The research aimed to understand how the receptor-binding specificity of these viruses has changed over time.

Upon investigation, it was observed that there is a recurrent preference for binding to 2,6-sialylated di-LacNAc N-glycans. In contrast, binding to 2,3-sialylated glycans was generally not detected. However, there are exceptions; the H1N1 strains A/Hongkong/117/1977 and A/New Caledonia/20/1999 exhibit binding to chicken tracheal tissues.

An interesting observation was made regarding the fluctuation in binding avidities among post-pandemic H1N1 viruses. The specific amino acids responsible for these changes have different effects on pre-pandemic HA proteins.

Furthermore, a classical egg-adapted H1N1 mutant was reported which demonstrated null binding across all testing platforms. This discovery underscores the role of RBS mutations during the initial adaptation and evolution of human H1N1 influenza viruses. These mutations impact the glycan-binding properties of these viruses, a feature that stands in contrast to H3N2 viruses which consistently bind glycans linked to avian erythrocyte hemagglutination.

These findings shed light on the significance of the RBS mutations in shaping the glycan-binding properties of H1N1 viruses.