In vivo analysis of the stability and fitness of variants recovered from foot-and-mouth disease virus quasispecies.
We have analysed the ability to infect pigs of two foot-and-mouth disease virus (FMDV) variants isolated at low frequencies from virus populations (quasispecies) generated in pigs on infection with a parental virus, C-S8c1. A monoclonal antibody-resistant mutant (MARM21), and a variant isolated at early times post-infection (S-3T1), each exhibiting a unique amino acid substitution in VP1, were able to cause disease in pigs, both by direct inoculation or by contact transmission. The symptoms developed were similar to those produced by C-S8c1 or the related virus C-S15c1. The VP1 sequence of viral RNA directly recovered from lesions of infected animals confirmed the stability of the variant genotypes. Pigs infected with S-3T1 consistently showed an advance of 12 to 24 h in the emergence of fever and lesions when compared to animals infected with C-S8c1 or the remaining variants, an observation consistent with its early isolation. The ability of FMDV variants to compete 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 overgrown by the parent. However, co-infection with C-S8c1 and MARM21 resulted in lesions in which C-S8c1 was predominant, indicating a selective disadvantage of this variant in swine. In contrast, lesions from swine co-infected with C-S8c1 and S-3T1 contained similar proportions of the two viruses. These results document fitness variations in vivo among components of the mutant spectrum of FMDV quasispecies.
Centro de Investigación en Sanidad Animal, INIA, Madrid, Spain.
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C
Carrillo
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Borca
D M
DM
Moore
D O
DO
Morgan
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Sobrino
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics* / Q000276:immunology; D005537:Aphthovirus / Q000235:genetics* / Q000276:immunology / Q000502:physiology*; D002213:Capsid / Q000235:genetics* / Q000276:immunology; D036022:Capsid Proteins; D002460:Cell Line; D006224:Cricetinae; D014644:Genetic Variation; D013552:Swine
D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; C442501:VP1 protein, Foot-and-mouth disease virus