Differential roles of two types of Glycans for cell attachment and entry of Merkel cell polyomavirus

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Merkel cell polyomavirus (MCPyV) is a causative agent of Merkel cell carcinoma (MCC) (Feng et al., 2008; Shuda et al., 2008). While in other polyomaviruses initial attachment (and sometimes entry) is mediated by sialylated glycoconjugates on the cells surface, MCPyV requires sulfated glycosaminoglycans (GAGs) for attachment and both sialic acid (Sia) and sulfated GAGs for efficient transduction of cultured cells (Neu et al., 2012; Schowalter et al., 2011). Here, we aim to decipher, on the molecular level, the individual roles that these different types of glycans play for MCPyV attachment and entry. Structural biology techniques (protein crystallography, NMR spectroscopy, and native mass spectrometry), cell-based infection assays, and sequence-defined glycooligomers will be combined to elucidate the molecular mechanisms that underlie the early steps of MCPyV infection. Because GAGs are large and naturally heterogeneous biomolecules, the project requires in-house production of chemically homogeneous oligosaccharides for structural biology experiments and functional studies. Our objectives therefore include methodological developments in the field of GAGs that will also be applicable to the study of other viruses that require GAGs for infection.