Effect of mutation on the virulence in mice of a strain of foot-and-mouth disease virus.

Twenty-eight mutations, representing mutation in five different polypeptide-coding regions of the foot-and-mouth disease genome, were examined for their effect on the virulence of the virus for suckling mice. Five types of mutation were examined: temperature-sensitive (ts), electrophoretic (e), co-variant temperature-sensitive and electrophoretic (ts/e), guanidine-resistant (gs+) and putative co-variant guanidine-resistant and electrophoretic (gs+/e). All the ts mutations and three out of the 11 non-ts mutations produced some reductions in virulence. In the majority of cases this reduction in virulence was shown to co-vary with the mutation. No correlation was observed between the site of a mutation or its 'cut-off' temperature and the extent of the reduction in virulence. Studies of the growth in vivo of a small selection of ts mutants suggested that for most mutants their reduced virulence was a trivial effect of their slow growth rate. With one exception they all eventually grew to parental virus levels, the resulting virus being temperature-sensitive and the disease indistinguishable from that caused by the parental virus. The one exception was an avirulent ts mutant which only grew to one-thousandth the titre of the parent virus. This mutant did not cause disease and was therefore considered to be the only avirulent mutant. Its mutation was in the coat protein-coding region of the genome, probably the region coding for VP3.