Antigenic properties and population stability of a foot-and-mouth disease virus with an altered Arg-Gly-Asp receptor-recognition motif

The antigenic properties and genetic stability of a multiply passaged foot- and-mouth disease virus (FMDV) clone C-S8c1 with an Arg-Gly-Gly trip(et (RG G) instead of the Arg-Gly-Asp (RGD) integrin-recognition motif at positions 141 to 143 of capsid protein VP1 are described. Clear antigenic difference s between FMDV RGG and clone C-S8c1 have been documented in ELISA, enzyme-l inked immunoelectrotransfer (Western) blot and neutralization assays using site A-specific monoclonal antibodies and anti-FMDV polyclonal antibodies f rom swine and guinea pigs. The results validate with a live virus the role of the RGD (in particular Asp-143) in recognition of land neutralization by ) antibodies, a role previously suggested by immunochemical and structural studies with synthetic peptides. The FMDV RGG was genetically stable in a l arge proportion of serial infections of BHK-21 cells. However, a revertant virus with RGD was generated in one out of six passage series. Interestingl y, this revertant FMDV did not reach dominance but established an equilibri um with its parental FMDV RGG, accompanied by an increase of quasispecies c omplexity at the sequences around the RGG triplet. FMDV RGG exhibited a sel ective disadvantage relative to other RGD-containing clones isolated from t he same parental FMDV population. The results suggest that large antigenic variations can be prompted by replacements at critical capsid sites, includ ing 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.