Picornavirus Structure Overview

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Abstract
In many cases, structures have been determined, often using the lower resolution cryo-electron microscopy (cryo-EM) technique, of picornaviruses in complex with their cellular receptors, neutralizing antibodies, antiviral compounds, or other, biologically significant ligands. Picornavirus capsids are assembled from 60 protomers, each composed of four structural proteins, viral protein 1 (VP1), VP2, VP3, and VP4. The first three of these proteins have molecular weights of around 30 kDa and form the external surface of the icosahedral shell. Conservation of three-dimensional structure is almost invariably greater than conservation of amino acid homology. Thus, structural comparisons can be used to trace divergent evolution over longer time spans than is possible by amino acid sequence comparisons. Assembly of picornaviruses proceeds from 6S protomers of VP1, VP3, and VP0, via 14S pentamers of five 6S protomers, to mature virions. The final step involves inclusion of the RNA into empty capsids or partially assembled shells with simultaneous cleavage of VP0 into VP2 and VP4. The mutant viruses that were able to grow were mostly single mutations and could be sorted into groups that were neutralized by the same set of antibodies. A variety of additional evidence all points to the ability of simple icosahedral viruses to be in constant flux or “breathing”. This unexpected and structurally difficult-to-understand phenomenon accounts for the virus being able to externalize the internal VP4 and amino-terminal region of VP1 in the initial stages of cell entry.