Influenza hemagglutinin - host sialic acid receptor complex (HA-SA receptor)

The interaction between the influenza virus hemagglutinin (HA) and host cell sialic acid receptors is the primary determinant of viral entry and host range. Hemagglutinin is a homotrimeric surface glycoprotein that recognizes and binds to terminal sialic acid residues on host cell surface glycoproteins and glycolipids, with human-adapted strains typically preferring alpha 2,6-linkages and avian strains preferring alpha 2,3-linkages (Skehel & Wiley, 2000, Annu Rev Biochem). Following attachment, the virus is internalized via endocytosis; the acidic environment of the endosome triggers a massive conformational change in HA that mediates the fusion of the viral envelope with the endosomal membrane, releasing the viral genome into the cytoplasm (Hamilton et al., 2012, Antiviral Res). As a critical step in the viral life cycle, this interaction is a major target for vaccines and therapeutic interventions, including neutralizing antibodies that block the binding site and small molecules like umifenovir that inhibit the fusion process (Blaising et al., 2014, Antiviral Res). Targeting the host receptor side, such as with the sialidase DAS181, provides an alternative strategy to prevent viral docking by enzymatically removing the sialic acid residues from the respiratory epithelium (Triana-Baltzer et al., 2015, PLOS ONE).

Other names

Influenza hemagglutininHASialic acid receptorHemagglutinin-sialic acid interactionViral attachment proteinH1N1 hemagglutininH3N2 hemagglutinin

Inhibition of viral attachment to host sialic acids, prevention of low-pH induced conformational changes required for membrane fusion, and enzymatic cleavage of host sialic acid receptors to prevent viral docking.