Two mechanisms of antigenic diversification of foot-and-mouth disease virus.

The amino acid replacements that underlay the diversification of the main antigenic site A (VP1 residues 138 to 150) of foot-and-mouth disease virus (FMDV) of serotype C have been identified. Sixteen new VP1 sequences of isolates from 1926 until 1989 belonging to subtypes C1, C2, C3, C4, C5, and unclassified are reported. The reactivities in enzyme-linked immunoelectrotransfer blot assays of capsid protein VP1 with a panel of neutralizing monoclonal antibodies that recognize sites A or C (the VP1 carboxy-terminus) have been correlated with the amino acid sequence at the relevant epitopes. The analyses involving the immunodominant site A reveal two mechanisms of antigenic change. One is a gradual increase in antigenic distance brought about by accumulation of amino acid replacements at two hypervariable segments within site A. A second mechanism consists of an abrupt antigenic change manifested by loss of many epitopes, caused by one replacement at a critical position (particularly Ala (145)----Val or His (146)----Gln). The identification of the amino acid substitutions responsible for such large antigenic changes provides new information for the design of synthetic anti-FMD vaccines. However, the screening of isolates from six decades suggests that the virus, even within the confines of a single serotype, has exploited a minimum of its potential for antigenic variation.