Glycan receptors of the Polyomaviridae: structure, function, and pathogenesis

• Polyomaviruses (PyV) bind to sialyated oligosaccharides on the host cell surface through interactions with the major capsid protein VP1.
• Structures of VP1–glycan complexes have now been solved for mouse, simian, and human PyVs.
• Structural and functional assays have identified sialylated glycosphingolipids, termed gangliosides, as important cell surface receptors for many PyVs.
• Alterations in VP1–glycan interactions can result in dramatic changes in PyV tropism and pathogenesis.

Multiple glycans have been identified as potential cell surface binding motifs for polyomaviruses (PyVs) using both crystallographic structural determinations and in vitro binding assays. However, binding alone does not necessarily imply that a glycan is a functional receptor, and confirmation that specific glycans are important for infection has proved challenging. In vivo analysis of murine polyomavirus (MPyV) infection has shown that subtle alterations in PyV–glycan interactions alone can result in dramatic changes in pathogenicity, implying that similar effects will be found for other PyVs. Our discussion will review the assays used for determining virus–glycan binding, and how these relate to known PyV tropism and pathogenesis.