ABSTRACT
The capsid of FMDV presents many neutralization epitopes that cluster in several exposed regions. One of the major antigenic sites involves the G-H loop of VP1, and two other major sites are defined by discontinuous epitopes that are structurally and functionally independent of that loop. The G-H loop appears as a mobile capsid element. In some virus strains this loop participates in discontinuous epitopes which may be disrupted by mutations in other capsid elements that stabilize alternative orientations of the G-H loop. In other virus strains the G-H loop delineates true continuous epitopes that can be faithfully mimicked by synthetic peptides with native-like conformational propensities, and that have been structurally and functionally characterized in detail. Some residues within this loop have a dual function in the interaction with the cell receptor and in direct recognition by many antibodies. Some of these neutralize infectivity through monovalent binding and steric inhibition of the interaction with the cell receptor. The cell attachment site of FMDV is not hidden from antibody attack, but it is protected from variation by the effect of negative selection. The extreme antigenic diversity of FMDV occur through multiple mutations, including a few critical ones, on the restricted subset of residues in each antigenic region that are involved in antibody binding, but that are not involved in other capsid functions.
