CIRCULAR-DICHROISM, MOLECULAR MODELING, AND SEROLOGY INDICATE THAT THE STRUCTURAL BASIS OF ANTIGENIC VARIATION IN FOOT-AND-MOUTH-DISEASE VIRUS IS ALPHA-HELIX FORMATION

Seven antigenic variants obtained from a single field isolate of foot- and-mouth disease virus, serotype A12, differ only at residues 148 and 153 in the immunodominant loop of viral protein VP1. Synthetic peptid es corresponding to the region 141-160 are highly immunogenic. UV circ ular dichroism shows that (i) in aqueous solution the peptides are nea rly identical, but in 100% trifluoroethanol they display helix-forming properties which correlate well with their serological crossreactivit ies for anti-peptide sera, and (ii) these properties are insensitive t o substitutions at position 153, except for proline, but are highly se nsitive to substitutions at position 148. This pattern can be explaine d by the effects of these substitutions on the amphiphilic character a nd positions of helices postulated in the region 146-156. Molecular mo dels indicate that residues 147, 148, 150, 151, 153-155, and 157 are m ost likely to interact with residues of the antibody paratopes. The da ta are consistent with the existence of an inverse gamma-turn around P ro-153, and a beta-turn at the cell-attachment site at residues 145-14 7.