Viral attachment strategies: the many faces of adenoviruses

The engagement of a cell-surface receptor by a virus is the first step in a complex process that culminates in the infection of the cell. Human adenoviruses are important pathogens that, depending on serotype, can utilize an impressive number of cellular receptors for attachment. Several structures of adenovirus attachment proteins in complex with their cognate ligands have been determined, enhancing our understanding of the underlying molecular recognition processes. Moreover, two new receptors for adenoviruses have also recently been identified. Using adenoviruses as an example, we examine the different attachment strategies that highly similar viral proteins within a single virus family can employ to engage different protein and carbohydrate receptors. For many viruses, consequences of such differences are altered tropism and pathogenicity. A better understanding of the parameters that determine specificity will therefore help to establish links between receptor tropism, spread, and disease. Moreover, it has relevance for the design and use of adenovirus-based gene delivery vehicles with improved properties and for the development of new antiviral strategies.

► We examine the attachment strategies of different adenovirus strains. ► We use crystal structures to compare adenovirus binding to different receptors. ► We define adenovirus protein regions required for receptor specificity. ► We identify adenovirus regions that enable switches in receptor binding. ► We predict interactions with a newly discovered adenovirus receptor.