RGD sequence of foot-and-mouth disease virus isessential for infecting cells via the natural receptor but can be bypassed by anantibody-dependent enhancement pathway.

Foot-and-mouth disease virus appears to initiateinfection by binding to cells at an Arg-Gly-Asp (RGD) sequence found in theflexible beta G-beta H loop of the viral capsid protein VP1. The role of the RGDsequence in attachment of virus to cells was tested by using syntheticfull-length viral RNAs mutated within or near the RGD sequence. Baby hamsterkidney (BHK) cells transfected with three different RNAs carrying mutationsbordering the RGD sequence produced infectious viruses with wild-type plaquemorphology; however, one of these mutant viruses bound to cells less efficientlythan wild type. BHK cells transfected with RNAs containing changes within theRGD sequence produced noninfectious particles indistinguishable from wild-typevirus in terms of sedimentation coefficient, binding to monoclonal antibodies,and protein composition. These virus-like particles are defined as ads- viruses,since they were unable to adsorb to and infect BHK cells. These mutants weredefective only in cell binding, since antibody-complexed ads- viruses were ableto infect Chinese hamster ovary cells expressing an immunoglobulin Fc receptor.These results confirm the essential role of the RGD sequence in binding offoot-and-mouth disease virus to susceptible cells and demonstrate that thenatural cellular receptor for the virus serves only to bind virus to thecell.