A single amino acid substitution affects multiple overlapping epitopes in the major antigenic site of foot-and-mouth disease virus of serotype C.
Neutralizing monoclonal antibodies (nMAbs) elicited against foot-and-mouth disease virus (FMDV) of serotype C were assayed with field isolates and variant FMDVs using several immunoassays. Of a total of 36 nMAbs tested, 23 recognized capsid protein VP1 and distinguished at least 13 virion conformation-independent epitopes involved in neutralization of FMDV C. Eleven epitopes of FMDV C-S8c1 have been located in segments 138-156 or 192-209 of VP1 by quantifying the reactivity of nMAbs with synthetic peptides and with nMAb-resistant mutants of FMDV C-S8c1 carrying defined amino acid substitutions. The main antigenic site of FMDV C-S8c1 (VP1 residues 138 to 150) consists of multiple (at least 10), distinguishable, overlapping epitopes. Some amino acid replacements abolished one of the epitopes, whereas other replacements affected several epitopes in this region. The conservative substitution His(146)----Arg, found in many nMAb-resistant mutants analysed, abolished the reactivity of the virus with all nMAbs that recognized epitopes in the main antigenic site of FMDV C-S8c1. This indicates that a minimum genetic change can result in a highly amplified phenotypic effect, as regards the antigenicity of FMDV.
Centro de Biología Molecular, Universidad Autónoma de Madrid, Spain.
M G
MG
Mateu
M A
MA
Martínez
L
L
Capucci
D
D
Andreu
E
E
Giralt
F
F
Sobrino
E
E
Brocchi
E
E
Domingo
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000956:Antigens, Viral / Q000235:genetics*; D005537:Aphthovirus / Q000145:classification / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000235:genetics*; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010455:Peptides / Q000138:chemical synthesis; D012703:Serotyping
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D000939:Epitopes; D007074:Immunoglobulin G; D010455:Peptides