ANTIGENIC HETEROGENEITY OF A FOOT-AND-MOUTH-DISEASE VIRUS SEROTYPE INTHE FIELD IS MEDIATED BY VERY LIMITED SEQUENCE VARIATION AT SEVERAL ANTIGENIC SITES

Antigenic variation in a major discontinuous site (site D) of foot-and -mouth disease virus (FMDV) of serotype C has been evaluated with neut ralizing monoclonal antibodies. Isolates representing the major evolut ionary sublines previously defined for serotype C were compared. Exten sive variation, comparable to that of continuous epitopes within the h ypervariable immunodominant site A (the VP1 G-H loop), was found. The amino acid sequences of the complete capsids of three antigenically hi ghly divergent FMDVs (C-1 Haute Loire-Fr/69, C-5 Argentina/69, and C-3 Argentina/85) have been determined and compared with the correspondin g sequences previously determined for seven additional type C viruses. Differences in antigenicity are due to a very limited number of subst itutions of surface amino acids accessible to antibodies and located w ithin antigenic sites previously identified on FMDV. A significant num ber of residues at these positions were also replaced in monoclonal an tibody escape mutants. Depending on the variants compared, replacement s within site A or at site D, or at both sites, contributed significan tly to their antigenic differences. Examples of divergence mediated by a few amino acid replacements were found among FMDVs of Europe and So uth America. The results suggest that within a serotype of FMDV, antig enically highly divergent viruses can arise in the field by very limit ed sequence variation at exposed key residues of each of several antig enic sites.