A second RGD motif in the 1D capsid protein of a SAT1 type foot-and-mouth disease virus field isolate is not essential for attachment to target cells

The amino acid sequence motif Arg-Gly-Asp (RGD), located in the surface-exposed beta G-beta H loop of the ID protein of different serotypes and subtypes of foot-and-mouth disease virus (FMDV), is highly conserved and participates in binding of FMDV to susceptible cells. Previous sequence analyses of the I D-encoding region of a FMDV serotype SAT I field isolate from Namibia (NAM/307/98) indicated the presence of a second RGD motif upstream of the conserved beta G-beta H loop RGD. The role of these RGD sequences in virus infection was investigated by mutating the beta G-beta H loop RGD to a KGE tripeptide, using a genome-length infectious chimeric cDNA clone. Although the infectivity of the derived mutant viruses for baby hamster kidney cells (BHK-21) was lost, subsequent replacement of the KGE sequence with RGD in the mutant cDNA clone led to recovery of infectious viruses. Furthermore, viral RNA replication could be demonstrated with the genetically engineered mutant and non-mutant viruses. The presence of virus particles in the transfected cells could be also demonstrated by electron microscopy. These results demonstrate that, in contrast to the beta G-beta H loop RGD motif, the second RGD sequence in the capsid protein ID of NAM/307/98 does not function as a ligand for receptor binding in BHK-21 cells. (c) 2006 Elsevier B.V. All rights reserved.