Similar to other non-enveloped viruses, the mechanism of cell entry for polyomaviruses is poorly understood. The polyomavirus capsid is an icosahedron composed of 72 pentamers of the major capsid protein VP1. There is one copy of minor capsid proteins, VP2 or VP3, at the center of each pentamer. According to previous studies, polyomavirus cell entry is a multi-step process which includes: 1) VP1 binding to sialic acid (SA) on the surface of host cells, 2) interaction of VP1 with alpha4beta1 integrin and 3) subsequent cell penetration. Biochemical studies have shown that SA alters polyomavirus protease sensitivity, suggesting a conformational change. The aim of this study was to determine these conformational changes at the molecular level. Therefore, we used single particle cryo-electron microscopy to construct 3D maps of wild type (WT) murine polyomavirus, WT bound to SA, a mutant with a disrupted integrin binding site, and the mutant bound to SA. Our results reveal that in both WT and mutant viruses, a significant conformational change happens after binding with SA which is seen as an additional ring of density inside the virus. Moreover some negative densities are seen in the difference map of WT and WT bound with SA, which suggests movement of some viral proteins after binding with SA.

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