The Cell Attachment Site on Foot-and-Mouth Disease Virus Includes the Amino Acid Sequence RGD (Arginine-Glycine-Aspartic Acid)

Abstract

SUMMARYThe amino acid sequence RGD (arginine-glycine-aspartic acid) is highly conserved in the VPI protein of foot-and-mouth disease virus (FMDV), despite being situated in the immunodominant hypervariable region between amino acids 135 and 160. RGDcontaining proteins are known to be important in promoting cell attachment in several different systems, and we report here that synthetic peptides containing this sequence are able to inhibit attachment of the virus to baby hamster kidney (BHK) cells. Inhibition was dose-dependent and could be reversed on removal of the peptide. A synthetic peptide corresponding to a portion of the same hypervariable region but not containing the RGD sequence did not inhibit virus attachment under the same conditions. Antibody against the RGD region of VPI blocked attachment of the virus to BHK cells, and neutralizing monoclonal antibodies, which neutralize virus by preventing cell attachment, were blocked by RGD-containing peptides from binding virus in an ELISA test. Cleavage of the C-terminal region of virus VP1 in situ with proteolytic enzymes reduced cell attachment, and antiserum against a peptide corresponding to this region was also able to inhibit attachment of virus to BHK cells. These results indicate that the amino acid sequence RGD at positions 145 to 147 and amino acids from the C-terminal region of VP1 (positions 203 to 213) contribute to the cell attachment site on FMDV for BHK cells.

Insights into neutralization of animal viruses gained from study of influenza virus

“…reovirus, rotavirus, rhinovirus and foot-and-mouth disease virus [37][38][39][40]) does inhibition of virus attachment fully account for the loss of infectivity observed under the particular conditions studied. Attachment of other viruses may be reduced by the binding of antibody but the magnitude of the reduction in attachment makes only a contribution to the neutralization found.…”

Structure and genomic organization of the ipiB and ipiO gene clusters of Phytophthora infestans

“…Moreover, in pathogenicity factors of some bacterial human pathogens, a functional RGD tripeptide was found to interact with integrins on the surface of host cells, thereby mediating uptake into the host cells (Finlay, 1990;Relman et al, 1990;Russell and Wright, 1988). The RGD tripeptide is also included in the attachment site of the foot-andmouth disease virus (Fox et al, 1989). In plants, RGDdependent cell wall-cell membrane adhesions have been demonstrated to occur (Schindler et al, 1989;Zhu et al, 1993) and proteins immunologically related to human vitronectin and its receptor have been detected (Quatrano et al, 1991;Sanders et al, 1991;Schindler et al, 1989).…”

An RNA virus can adapt to the multiplicity of infection.

“…1). The G-H loop of VP1 is involved in recognition of an integrin receptor via an Arg-GlyAsp triplet (Fox et al, 1989 ;Mason et al, 1994 ;Berinstein et al, 1995 ;Herna! ndez et al, 1996 ;Jackson et al, 1997 ;Neff et al, 1998) and it forms a major antigenic site of the virus which for FMDV of serotype C has been termed site A (Mateu, 1995).…”