Structures of foot and mouth disease virus pentamers: Insight into capsid dissociation and unexpected pentamer reassociation

This is the first structure of dissociated pentamers for FMDV, and indeed for any picornavirus. We also present the first visualization of a picornavirus particle assembled from pentamers comprising VP1, 2 and 3. The formation of regular assemblies rather than random aggregates has enabled us to solve the structure to relatively high resolution using cryo-electron microscopy. Overall there are remarkably few large-scale conformational changes in the dis-assembled pentamer from its structure in the intact virion, suggesting that the mature virus pentamer is essentially a stable endpoint. However, a small rotation in VP3 abrogates the usual pentamer interface and together with the lack of VP4 drives the abnormal inside-out association of these pentameric subunits, rather than the correct capsid assembly. This change in conformation of the dis-assembled pentamer changes the antigenic surface and presumably underlies, in part, the loss of efficacy of vaccines if native particle integrity is destroyed.