Structural and Functional Analysis of Murine Polyomavirus Capsid Proteins Establish the Determinants of Ligand Recognition and Pathogenicity

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Viruses are obligate intracellular pathogens, and all of them share one crucial step in their life cycle—the attachment to their host cell via cellular receptors, which are usually proteins or carbohydrates. This step is decisive for the selection of target cells and virus entry. In this study, we investigated murine polyomavirus (MuPyV), which attaches to host gangliosides with its major capsid protein, VP1. We have solved the crystal structures of VP1 in complex with previously known interaction partners as well as with the ganglioside GT1a, which we have identified as a novel functional receptor for MuPyV. Earlier studies have shown that different strains with singular amino acid exchanges in the receptor binding pocket of VP1 display altered pathogenicity and viral spread. Our investigations show that, while these exchanges do not abolish binding or significantly alter interaction modes to our investigated carbohydrates, they have subtle effects on glycan affinity. The combination of receptor specificity, abundance, and affinity reveals a much more intricate regulation of pathogenicity than previously believed. Our results exemplify how delicate changes to the receptor binding pocket of MuPyV VP1 are able to drastically alter virus behavior. This system provides a unique example to study how the first step in the life cycle of a virus can dictate its biological properties.

Vyšlo v časopise: Structural and Functional Analysis of Murine Polyomavirus Capsid Proteins Establish the Determinants of Ligand Recognition and Pathogenicity. PLoS Pathog 11(10): e32767. doi:10.1371/journal.ppat.1005104
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005104

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