Glycan Engagement by Viruses: Receptor Switches and Specificity

A large number of viruses, including many human pathogens, bind cell-surface glycans during the initial steps of infection. Viral glycan receptors such as glycosaminoglycans and sialic acid–containing carbohydrates are often negatively charged, but neutral glycans such as histo–blood group antigens can also function as receptors. The engagement of glycans facilitates attachment and entry and, consequently, is often a key determinant of the host range, tissue tropism, pathogenicity, and transmissibility of viruses. Here, we review current knowledge about virus-glycan interactions using representative crystal structures of viral attachment proteins in complex with glycans. We illuminate the determinants of specificity utilized by different glycan-binding viruses and explore the potential of these interactions for switching receptor specificities within or even between glycan classes. A detailed understanding of these parameters is important for the prediction of binding sites where structural information is not available, and is invaluable for the development of antiviral therapeutics.