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.
Martínez
M A
MA
Centro de Biología Molecular (CSIC-UAM), Universidad Autónoma de Madrid, Spain.
Hernández
J
J
Piccone
M E
ME
Palma
E L
EL
Domingo
E
E
Knowles
N
N
Mateu
M G
MG
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000940:Antigenic Variation; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology*; D005537:Aphthovirus / Q000145:classification / Q000276:immunology*; D002213:Capsid / Q000737:chemistry / Q000276:immunology; D008969:Molecular Sequence Data; D012703:Serotyping; D014765:Viral Vaccines / Q000276:immunology
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D014765:Viral Vaccines