ANTIGENICALLY PROFOUND AMINO-ACID SUBSTITUTIONS OCCUR DURING LARGE POPULATION PASSAGES OF FOOT-AND-MOUTH-DISEASE VIRUS

Foot-and-mouth disease virus (FMDV) with amino acid substitutions next to the highly conserved R-G-D motif were isolated following large pop ulation passages of the virus (N. Sevilla and E. Domingo, 1996, J. Vir ol, in press). Reactivity with a panel of monoclonal antibodies which recognize different epitopes within site A was abolished or highly dim inished in the mutants. This provides direct evidence of a drastic ant igenic change occurring in the absence of selection by antibodies. Mol ecular modeling studies predict only minor alterations in the conforma tion of the G-H loop of VP1 and the R-G-D motif in these mutants. None of these variants became dominant in many serial infections involving smaller FMDV population numbers. In addition to documenting profound antigenic variation without immune selection, the results suggest that the repertoire of antigenic variants evolving in viral quasispecies m ay be greatly influenced by the population size of the virus. (C) 1996 Academic Press, Inc.