IN-VIVO ANALYSIS OF THE STABILITY AND FITNESS OF VARIANTS RECOVERED FROM FOOT-AND-MOUTH-DISEASE VIRUS QUASI-SPECIES

We have analysed the ability to infect pigs of two foot-and-mouth dise ase virus (FMDV) variants isolated at low frequencies from virus popul ations (quasispecies) generated in pigs on infection with a parental v irus, C-S8c1, A monoclonal antibody-resistant mutant (MARM21), and a v ariant isolated at early times post-infection (S-3T(1)), each exhibiti ng a unique amino acid substitution in VP1, were able to cause disease in pigs, both by direct inoculation or by contact transmission. The s ymptoms developed were similar to those produced by C-S8c1 or the rela ted virus C-S15c1, The VP1 sequence of viral RNA directly recovered fr om lesions of infected animals confirmed the stability of the variant genotypes. Rigs infected with S-3T(1) consistently showed an advance o f 12 to 24 h in the emergence of fever and lesions when compared to an imals infected with C-S8c1 or the remaining variants, an observation c onsistent with its early isolation. The ability of FMDV variants to co mpete in vivo with C-S8c1 was investigated in co-infection experiments . Analysis of the proportion of each of the competitors in lesions of co-infected pigs revealed that none of the variants was completely ove rgrown by the parent. However, co-infection with C-S8c1 and MARM21 res ulted in lesions in which C-S8c1 was predominant, indicating a selecti ve disadvantage of this variant in swine. In contrast, lesions from sw ine coinfected with C-S8c1 and S-3T(1) contained similar proportions o f the two viruses. These results document fitness variations in vivo a mong components of the mutant spectrum of FMDV quasispecies.