Investigating virus–glycan interactions using glycan microarrays

•Glycan microarrays have revolutionized studies of protein–glycan interactions and are used to define specificity of glycan binding proteins.•Glycan microarrays are used to explore glycan recognition by viruses, such as rotaviruses and influenza viruses.•Functional glycomics using shotgun glycan microarrays of endogenous glycans can identify cellular glycans that bind viruses.•Glycan microarrays can help to identify potential glycans that may be important for virus attachment and entry.•An array of >240 human milk glycans representing a portion of the human milk free glycan glycome is now available for interrogation.

While all viruses must transit the plasma membrane of mammalian cells to initiate infection, we know little about the complex processes involved in viral attachment, which commonly involve recognition of glycans by viral proteins. Glycan microarrays derived from both synthetic glycans and natural glycans isolated through shotgun glycomics approaches provide novel platforms for interrogating diverse glycans as potential viral receptors. Recent studies with influenza and rotaviruses using such glycan microarrays provide examples of their utility in exploring the challenging questions raised in efforts to define the complex mechanistic protein–glycan interactions that regulate virus attachment to host cells.