title: Antigenic heterogeneity of a foot-and-mouth disease virus serotype in the field is mediated by very limited sequence variation at several antigenic sites.
abstract: Antigenic variation in a major discontinuous site (site D) of foot-and-mouth disease virus (FMDV) of serotype C has been evaluated with neutralizing monoclonal antibodies. Isolates representing the major evolutionary sublines previously defined for serotype C were compared. Extensive variation, comparable to that of continuous epitopes within the hypervariable immunodominant site A (the VP1 G-H loop), was found. The amino acid sequences of the complete capsids of three antigenically highly divergent FMDVs (C1 Haute Loire-Fr/69, C5 Argentina/69, and C3 Argentina/85) have been determined and compared with the corresponding sequences previously determined for seven additional type C viruses. Differences in antigenicity are due to a very limited number of substitutions of surface amino acids accessible to antibodies and located within antigenic sites previously identified on FMDV. A significant number of residues at these positions were also replaced in monoclonal antibody escape mutants. Depending on the variants compared, replacements within site A or at site D, or at both sites, contributed significantly to their antigenic differences. Examples of divergence mediated by a few amino acid replacements were found among FMDVs of Europe and South America. The results suggest that within a serotype of FMDV, antigenically highly divergent viruses can arise in the field by very limited sequence variation at exposed key residues of each of several antigenic sites.
authors.affiliation: Centro de Biología Molecular (CSIC-UAM), Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
authors.forename: M G
authors.initials: MG
authors.lastname: Mateu
authors.forename: J
authors.initials: J
authors.lastname: Hernández
authors.forename: M A
authors.initials: MA
authors.lastname: Martínez
authors.forename: D
authors.initials: D
authors.lastname: Feigelstock
authors.forename: S
authors.initials: S
authors.lastname: Lea
authors.forename: J J
authors.initials: JJ
authors.lastname: Pérez
authors.forename: E
authors.initials: E
authors.lastname: Giralt
authors.forename: D
authors.initials: D
authors.lastname: Stuart
authors.forename: E L
authors.initials: EL
authors.lastname: Palma
authors.forename: E
authors.initials: E
authors.lastname: Domingo
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D005537:Aphthovirus / Q000145:classification / Q000235:genetics / Q000276:immunology*; D002213:Capsid / Q000235:genetics / Q000276:immunology*; D036022:Capsid Proteins; D014644:Genetic Variation; D016056:Immunodominant Epitopes; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D012703:Serotyping
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; D016056:Immunodominant Epitopes; C442501:VP1 protein, Foot-and-mouth disease virus