Title:  Sweet Viral Evolution: Using computation to understand the selective pressures shaping viral envelope glycosylation
Abstract:  Envelope glycoproteins play a central role in mediating host-cell recognition and membrane fusion in enveloped viruses; as the only exposed viral component, the extraviral domains of these glycoproteins are primary targets of the humoral immune response. These selective pressures have led many viral glycoproteins to display a so-called "glycan shield," a layer of host-form oligosaccharides that mask the foreign nature of the viral particle. While the general concept of the glycan shield has been well established for some time, there remain many open questions as to how it is shaped. We have been developing computational tools to investigate these questions in the the context of the HIV envelope glycoproteins gp120/gp41. Our approach combines structural biology, traditional methods of analyzing conservation in multiple sequence alignments, novel approaches to understanding feature conservation in unalignable-sequences, and biochemical reaction network modeling of the cellular glycosylation machinery.