David Rowlands collection

Antibodies to a synthetic peptide corresponding to the 141 to 160 amino acid sequence of the protein VP1 of type O foot-and-mouth disease virus (FMDV) neutralize a wider range of type O isolates than anti-virion serum. Extending this peptide at the amino terminus reduced the number of strains neutralized by the anti-peptide sera. Reactions with antisera to peptides representing non-contiguous native sequences showed that it was also possible to increase the number of strains effectively neutralized. Selected substitutions of a single amino acid at position 148 markedly altered the neutralizing specificity of antibodies elicited by the 141 to 160 peptide. In particular, a peptide with an L → S substitution at this position induced antibodies which neutralized a type O and a type A virus equally, and guinea-pigs inoculated with it were protected from challenge with either virus. Attempts to isolate variant viruses resistant to neutralization with anti-peptide antibody indicated that these occurred at low frequency, and there was some evidence that resistance may be partially conferred by mutations outside the peptide sequence.

The 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 % of the residues of VP 1, 15 % 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 VP1, 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 VP1 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.