Rapid evolution of foot-and-mouth disease virus (FMDV) is documented during persistent infections of cattle. The carrier state was established experimentally with plaque-purified FMDV of serotype C3. Virus was recovered from the esophageal pharyngeal area of the animals up to 539 days postinfection. Analysis of capsid proteins by electrofocusing and by electrophoretic mobility of the genomic poly(C)-rich tract suggested heterogeneity in several isolates and sequential dominance of viral subpopulations. Nucleotide sequences of the VPI-coding region of the parental FMDV C3 clones and of seven isolates from the carrier cattle showed point mutations that represented rates of fixation of mutations of 0.9 x 10-2 to 7.4 x 10-2 substitutions per nucleotide per year; 59% of the base changes led to amino acid substitutions, some of which were located within residues 135 to 151, a region involved in neutralization of FMDV. In the esophageal pharyngeal fluid samples, FMDV C3-neutralizing activity was present. Antigenic variation was demonstrated with monoclonal antibodies raised against FMDV C3. Two isolates from carrier cattle differed from the parental virus by 102_ or 103-fold decreased reactivity with neutralizing monoclonal antibodies. We suggest that persistent, inapparent infections of ruminants, in addition to being a reservoir of virus, may promote the rapid selection of antigenically variant FMDVs.

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No differences were observed between cattle and Indian buffalo (Bubalus bubalis) in terms of temperature, viraemia or virus replication in the pharyngeal area, during the acute phase of foot-and-mouth disease. Like cattle, the Indian buffalo became infected and excreted virus before any clinical signs of foot-and-mouth disease developed. The disease was transmitted from cattle to buffalo and vice versa, during the acute stage of infection, as if the animals had been of the same species, presumably because of their close phylogenetic relationship. There were more tongue lesions in the cattle than in the buffalo. Foot lesions in the buffalo at first had a scaley appearance, but later became vesicular. Anti-virus infection associated antigen and neutralising antibodies were synthesised at the same time in both species and reached similar titres in the same period. Persistent infection in the buffalo during the first 35 days after infection was similar to that in the cattle.

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