Figure 4. Bridging glycan-binding specificity with biological function of influenza A virus.

A, Lectin staining of human upper respiratory tissues provides a high-level picture of α2-3- and α2-6- N- and O-linked glycans. B, Finer granularity on the physiological glycans is obtained by analyzing glycans derived from upper respiratory epithelial cells using a combination of analytical tools. C, The biochemical specificity of HA-glycan interactions is characterized based on binding of recombinant HA or whole viruses to glycan structures presented using a glycan array platform. The array platform is designed to incorporate target structures based on their predominant expression in the upper respiratory tissues. D, The high throughput data on binding of HA or virus to hundreds of glycans on the array is captured into a relational database and this data is mined using data mining methods to obtain rules or classifiers that govern the glycan-binding specificity of WT and mutant HAs. E, The rules obtained from data mining are corroborated using X-ray co-crystal structures of HA-glycan complexes and molecular simulation of HA-glycan interactions. The comprehensive knowledge of the key determinants of HA-glycan interactions obtained using this integrated framework provides a much better handle to correlate with the biological function of host adaptation of the influenza A virus.