Surface Structure and RNA-Protein Interactions of Foot-and-Mouth Disease Virus

Abstract

SUMMARYThe surface structure of foot-and-mouth disease virus (FMDV) and the interaction of the individual capsid proteins with the virus RNA have been examined using modification reagents. By measuring the extent of modification of the lysine residues of intact and disrupted virus particles and the 12S protein subunit with Bolton & Hunter reagent it was found that 54~o of the residues of VP 1, 15 ~o of the residues of VP2 and 37~ of the residues of VP3, equivalent to five, two and four lysine residues respectively, are on the surface of the intact virus particle. Polypeptide VP4 was not modified in intact virus particles, indicating that it has no lysine residues on the surface of the virus. Modification with sodium metabisulphite, which causes a specific transamination reaction between cytidylic acid residues in ssRNA and closely associated basic amino acids, cross-linked all four structural proteins to the virus RNA. Both fragments of VPI, produced by treatment of the virus particle with trypsin, are also cross-linked to the RNA. These observations have been combined with the evidence that the immunogenic activity of VP 1 may be contained in two discontinuous sites, at amino acids 141 to 160 and 200 to 213, in proposing a model for the arrangement of this polypeptide in the virus particle.

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

“…Also the enzymic cleavage of this region abolished cell attachment, implying that its contribution is not merely through a steric effect on the RGD site. Predictive models of VP 1 structure have placed the RGD region and the C-terminal region of VP 1 in close proximity on the virus surface (B. H. Nicholson, personal communication; Morrell et al, 1987), but whether amino acids from the C-terminal region contribute directly to attachment, or indirectly by providing conformational support for the RGD site, is not clear. In either case variations in this region may be responsible for the different receptor specificities amongst FMDV strains.…”

Neutralizing Epitopes of Type O Foot-and-Mouth Disease Virus. II. Mapping Three Conformational Sites with Synthetic Peptide Reagents

“…The possibility that the two immunogenic tracts are closely juxtaposed in the tertiary structure of the VP1 molecule was originally proposed by Morrell (1983) on the basis of cross-linking studies. The first serological evidence that they both contributed to a single antigenic domain was presented in a preliminary communication of some of the data included here (Parry et al, 1985).…”

Host Cell Selection of Antigenic Variants of Foot-and-Mouth Disease Virus

“…Amino acids at the C terminus of the protein have also been implicated and studies with MAbs to a virus of the O serotype of FMDV suggest that the two regions of the protein together form a conformational epitope on the virus surface (Parry et al, 1985;Morrell et al, 1987). Different FMDV isolates contain a variety of trypsin-sensitive residues within these sequences but in all cases enzyme treatment of intact virus particles results in cleavage of VP1 in these regions.…”