Structural analysis of evolutionary origins of influenza hemagglutinin and other viral lectins

Influenza and other viruses use host-cell-surface sugars as receptors. Here we show that the sugar-binding domains in influenza hemagglutinin and other viral lectins share the same structural fold as human galectins (host lectins). Unlike the easily accessible sugar-binding sites in human galectins, the sugar-binding sites in viral lectins are hidden in cavities. We propose that these viral lectins originated from host lectins but have evolved to use hidden sugar-binding sites to evade host immune attacks.