Membrane environment can enhance the interaction of glycan binding protein to cell surface glycan receptors.

The binding of lectins to glycan receptors on the host cell surface is a key step contributing to the virulence and species specificity of most viruses. This is exemplified by the viral protein hemagglutinin (HA) of the influenza A virus, whose binding specificity is modulated by the linkage pattern of terminal sialic acids on glycan receptors of host epithelial cells. Such specificity dictates whether transmission is confined to a particular animal species or jumps between species. Here, we show, using H5N1 avian influenza as a model, that the specific binding of recombinant HA to α2-3 linked sialic acids can be enhanced dramatically by interaction with the surface of the lipid membrane. This effect can be quantitatively accounted for by a two-stage process in which weak association of HA with the membrane surface precedes more specific and tighter binding to the glycan receptor. The weak protein-membrane interaction discovered here in the model system may play an important secondary role in the infection and pathogenesis of the influenza A virus.