Influenza virus-glycan interactions

Abstract

It has been known for many years that influenza viruses bind by their hemagglutinin surface glycoprotein to sialic acid (N-acetylneuraminic acid) on the surface of the host cell, and that avian viruses most commonly bind to sialic acid linked α2-3 to galactose while most human viruses bind to sialic acid in the α2-6 configuration. Over the past few years there has been a large increase in data on this binding due to technological advances in glycan binding assays, reverse genetic systems for influenza and in X-ray crystallography. The results show some surprising changes in binding specificity that do not appear to affect the ability of the virus to infect host cells.

Figure 1

Simplified schematic of how binding by human H3N2 viruses has changed over the years. The figure shows the phylogenetic tree of HA based on amino acid sequence from 1968 (bottom left) to 2012 (top right) with sample structures of glycans that are bound. Binding data is from the CFG Glycan Array v5.1 [14] and the tree was generated at https://flu.lanl.gov/ [28].

Figure 2

Examples of binding by human H3N2 isolates that diverge from the pattern shown in Figure 1. The boxes represent each virus from 1968 (left) to 2010 (right). Binding is color coded as percent of the highest signal, from 100% (red) through 50% (green) to 10% (violet) with white representing <10%. These are the highest-binding glycans for the strains in years indicated. Data from Gulati et al. [14].