The genetics of foot and mouth disease virus

Abstract

Work on the genetics of foot-and-mouth disease virus is reviewed, with particular emphasis on mutation and recombination as possible mechanisms of change in the virus and on the use of genetics to analyse the functions of the genome. The mutation rate has been shown to be similar to that of other RNA viruses and the regions of the genome in which mutation is tolerated are described. Work has begun on studying the accumulation of mutations under field conditions; the fac tors affecting this are clearly complex and cannot be attributed directly to par ticular hosts or the presence of antibody. Recombination has been shown to occur in tissue culture in the laboratory between even the most distantly related serotypes. It does not require specific nucleotide sequences or extensive homology and oc curs in many mixedly infected cells. Therefore, given the opportunity and favourable selective conditions, it has the potential to produce large shifts in the phenotype of the virus. Genetic techniques have been applied to the analysis of RNA replica tion and capsid structure. In RNA replication, the role of p56a as the viral polymerase has been confirmed and the involvement of another non-structural pro tein (p34) has been demonstrated. Monoclonal antibodies have been used to isolate neutralisation-resistant mutants of a type O virus for which analysis has defined three non-overlapping antigenic sites on the capsid.

Crossover regions in foot-and-mouth disease virus (FMDV) recombinants correspond to regions of high local secondary structure

“…As the recombination zones analysed [14,21,29] are of different size, new programs were written to sum directly all secondary structure scores above a Total secondary structure scores per interval were obtained by adding together all percentage matches above 62 percent occurring in the zones of length indicated by nucleotide interval along the diagonal, and of 50 nucleotides width to each side. In Column 5 the ratios of total secondary structure score over number of nucleotides are given.…”

“…In general it was found that the mean value of potential secondary structure is significantly higher in crossover zones than in recombination-free zones. Recombination increased much more steeply with increasing secondary structure in the part of the genome coding for non-structural proteins than in the 5' third of the genome coding for structural proteins.Homologous recombination in viruses with non-segmented RNA genomes was recognized in early studies using genetic markers [9,18,25], and a considerable amount of genetic evidence for recombination of picornaviruses had accumulated [4,5,13,21] before its existence was confirmed biochemically by protein and oligonucleotide separation techniques [14,28,29,31] and more recently by genome sequence data [15,27,32]. As well as in picornaviruses, recombination has recently been found to occur in coronaviruses [10,19] and in the genome of a multipartite plant virus [2].…”

“…The nucleotide sequence of 94 percent of the genomic RNA of FMDV has been determined by Forss et al [7]; this sequence spans the RNA between the 5' proximal poly (C) tract and the 3' terminal poly (A) tail. FMDV recombinants have been extensively characterized since Pringle's [25] original observation, and McCahon's group has recently mapped the crossover sites of 17 classes of FMDV recombinants using biochemical techniques [14,21,22,29]. In their analysis of oligonucleotides of recombinants Saunders et al [29] used the numbering system of Forss et at.…”