Effect of Mutation on the Virulence in Mice of a Strain of Foot-and-Mouth Disease Virus

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Abstract
Twenty-eight mutations, representing mutation in 5 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-varient temperature-sensitive and electrophoretic (ts/e), guanidine-resistant (gs+) and putative co-variant guanidine-resistant and electrophoretic (gs+/e). All the ts mutations and 3 of the 11 non-ts mutations produced some reductions in virulence. This reduction in virulence generally co-varied 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 1 exception they all eventually grew to parental virus levels, the resulting virus being ts and the disease indistinguishable from that caused by the parental virus. The 1 exception was an avirulent ts mutant which only grew 1/1000 the titer of the parent virus. This mutant did not cause disease and was thus 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.