title: Antigenic properties and population stability of a foot-and-mouth disease virus with an altered Arg-Gly-Asp receptor-recognition motif.
abstract: The antigenic properties and genetic stability of a multiply passaged foot-and-mouth disease virus (FMDV) clone C-S8c1 with an Arg-Gly-Gly triplet (RGG) instead of the Arg-Gly-Asp (RGD) integrin-recognition motif at positions 141 to 143 of capsid protein VP1 are described. Clear antigenic differences between FMDV RGG and clone C-S8c1 have been documented in ELISA, enzyme-linked immunoelectrotransfer (Western) blot and neutralization assays using site A-specific monoclonal antibodies and anti-FMDV polyclonal antibodies from swine and guinea pigs. The results validate with a live virus the role of the RGD (in particular Asp-143) in recognition of (and neutralization by) antibodies, a role previously suggested by immunochemical and structural studies with synthetic peptides. The FMDV RGG was genetically stable in a large proportion of serial infections of BHK-21 cells. However, a revertant virus with RGD was generated in one out of six passage series. Interestingly, this revertant FMDV did not reach dominance but established an equilibrium with its parental FMDV RGG, accompanied by an increase of quasispecies complexity at the sequences around the RGG triplet. FMDV RGG exhibited a selective disadvantage relative to other RGD-containing clones isolated from the same parental FMDV population. The results suggest that large antigenic variations can be prompted by replacements at critical capsid sites, including those involved in receptor recognition. These critical replacements may yield viruses whose stability allows them to replicate efficiently and to expand the sequence repertoire of an antigenic site.
authors.affiliation: Centro de Biología Molecular 'Severo Ochoa', Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28049 Madrid, Spain1.
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Ruiz-Jarabo
authors.affiliation: Centro de Biología Molecular 'Severo Ochoa', Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28049 Madrid, Spain1.
authors.forename: Noemí
authors.initials: N
authors.lastname: Sevilla
authors.affiliation: Centro de Biología Molecular 'Severo Ochoa', Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28049 Madrid, Spain1.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Dávila
authors.affiliation: Centro de Biología Molecular 'Severo Ochoa', Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28049 Madrid, Spain1.
authors.forename: Gema
authors.initials: G
authors.lastname: Gómez-Mariano
authors.affiliation: Centro de Biología Molecular 'Severo Ochoa', Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28049 Madrid, Spain1.
authors.forename: Eric
authors.initials: E
authors.lastname: Baranowski
authors.affiliation: Centro de Biología Molecular 'Severo Ochoa', Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28049 Madrid, Spain1.
authors.forename: Esteban
authors.initials: E
authors.lastname: Domingo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D005537:Aphthovirus / Q000235:genetics / Q000276:immunology*; D001120:Arginine / Q000235:genetics / Q000276:immunology; D001224:Aspartic Acid / Q000235:genetics / Q000276:immunology; D001665:Binding Sites; D002213:Capsid / Q000235:genetics / Q000276:immunology*; D036022:Capsid Proteins; D002460:Cell Line; D006224:Cricetinae; D005998:Glycine / Q000235:genetics / Q000276:immunology; D006168:Guinea Pigs; D016023:Integrins / Q000378:metabolism; D008969:Molecular Sequence Data; D011991:Receptors, Virus / Q000378:metabolism; D013552:Swine
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; D016023:Integrins; D011991:Receptors, Virus; C442501:VP1 protein, Foot-and-mouth disease virus; D001224:Aspartic Acid; D001120:Arginine; D005998:Glycine