DIFFERENTIAL RESTRICTIONS ON ANTIGENIC VARIATION AMONG ANTIGENIC SITES OF FOOT-AND-MOUTH-DISEASE VIRUS IN THE ABSENCE OF ANTIBODY SELECTION

Clonal populations of foot-and-mouth disease virus have been serially passaged in cell culture to analyse variation in the absence of immune selection at different antigenic sites of the virus. Mutant frequenci es at the RNA regions encoding two independent antigenic sites (sites C and D) were more than twentyfold lower than for antigenic site A (th e G-H loop of VP1). Correspondingly, fixation of amino acid substituti ons was very restricted in sites C and D. In spite of such a restricti on, neutralization assays using fractionated anti-virus polyclonal ant ibodies has provided direct evidence of significant antigenic variatio n in the absence of immune selection at sites unrelated to site A. It is proposed that the degree of tolerance to acceptance of amino acid r eplacements may modulate the variation at different antigenic epitopes of the same virus.