The structure and function of a foot-and-mouth disease virus-oligosaccharide receptor complex

Heparan sulfate has an important role in cell entry by foot-and mouth disea se virus (FMDV), We find that subtype O-1 FMDV binds this glycosaminoglycan with a high affinity by immobilizing a specific highly abundant motif of s ulfated sugars. The binding site is a shallow depression on the virion surf ace, located at the junction of the three major capsid proteins, VPI, VP2 a nd VP3. Two pre-formed sulfate-binding sites control receptor specificity. Residue 56 of VP3, an arginine in this virus, is critical to this recogniti on, forming a key component of both sites. This residue is a histidine in h eld isolates of the virus, switching to an arginine in adaptation to tissue culture, forming the high affinity heparan sulfate-binding site. We postul ate that this site is a conserved feature of FMDVs, such that in the infect ed animal there is a biological advantage to low affinity, or more selectiv e, interactions with glycosaminoglycan receptors.