Attachment strategies of glycan-binding viruses
Virus attachment to cells initiates infection and is also a key determinant of host range, tissue tropism and pathogenesis. Carbohydrates such as sialic acid are prominently displayed on many cell surfaces, and they are frequently used by many viruses as their initial, and sometimes only, attachment receptors. Understanding how viruses engage sialic acid is essential for combating infection and designing improved therapeutic viral vectors. Recent advances in studies of virus-glycan interactions have made it possible to rapidly identify specific receptors using glycan array screening, define the atomic level structure of virus-glycan interactions using crystallography, and generate recombinant viruses or pseudoviruses to rationalize the effect of glycan binding in cell entry, tissue tropism, and disease pathogenesis.
I will report on the current state of our ongoing effort to define the receptor binding properties of human polyomaviruses, adenoviruses and coxsackieviruses. All three pathogens use sialylated glycan receptors for their cell attachment. In combination with mutagenesis experiments and functional studies, structural analyses have enabled us to understand the determinants of specificity in each case. Exploitation of these determinants provides an excellent platform for the development of antiviral agents. We are also able to show that receptor specificities can be switched through subtle changes in the binding pockets, demonstrating the dynamic aspects of virus interactions with receptors.
Thilo Stehle is Professor and Head of the Biochemistry Institute at the University of Tübingen, furthermore Adjunct Professor in Pediatrics at Vanderbilt University School of Medicine.
Stehle started his scientific career as Chemistry student at the University of Freiburg, from which he also obtained his PhD in 1992 for the analysis of the structure and reaction mechanism of enzymes. He stayed in the field of structural biology for his Post-Doc and joined Stephen Harrison at Harvard University, where he elucidated the structure of complete virus particles. In 1997, Stehle established his own group at Harvard Medical School. This was the starting point for his still ongoing research about interactions between viruses and receptors on the molecular and structural level. In early 2005, Stehle moved to Tübingen and took up his current position.
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