SYSTEMATIC REPLACEMENT OF AMINO-ACID-RESIDUES WITHIN AN ARG-GLY-ASP-CONTAINING LOOP OF FOOT-AND-MOUTH-DISEASE VIRUS AND EFFECT ON CELL RECOGNITION

The conserved Arg-Gly-Asp (RGD) motif found in a hypervariable, mobile antigenic loop of foot-and-mouth disease virus (FMDV) is critically i nvolved in virus attachment to cells by binding to an integrin, probab ly related to alpha(nu)beta(3). Here we describe (i) the synthesis of 241 15-mer peptides, which represent this loop of FMDV (isolate C-S8c1 ) and single variants in which each amino acid residue was replaced by 16 others and (ii) the inhibitory activity of these peptides on the a bility of FMDV C-S8c1 to recognize and infect susceptible cells. This approach has allowed a first detailed evaluation of the specificity of each residue within a RGD containing protein loop on cell recognition . The results indicate that, in addition to the exquisitely specific R GD triplet, two highly conserved Leu residues located at positions +1 and +4 downstream of the RGD and, to a lesser extent, the residue at p osition +2 are the only critical and specific determinants within the loop in promoting cell recognition of a viral ligand. The results supp ort the proposal that, in spite of their involvement in antibody recog nition, RGD and other FMDV loop residues are remarkably conserved beca use of their essential role in cell recognition.