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 triplet (RGG) instead of the Arg-Gly-Asp (RGD) integrinrecognition
motif at positions 141 to143 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 RGDcontaining
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.