Multiple genetic variants arise in the course of replication of foot-and-mouth disease virus in cell culture

Abstract

The genetic heterogeneity generated upon passage of foot-and-mouth disease virus (FMDV) in cell culture has been evaluated by T1-oligonucleotide fingerprinting of genomic RNA. Plaque-purified FMDV O-S7 and C-S8 were propagated by serial low multiplicity infections of BHK-21 (c-13) or IBRS-2 (c-26) cells. In independent parallel passage of the same virus, different oligonucleotide variations were fixed in the RNAs. T1-oligonucleotide fingerprinting of RNA from 34 individual viral clones derived from two passaged populations shows an extensive heterogeneity, with some mutations present in only one of the cloned genomes analyzed. Some FMDV variants are phenotypically distinct in that they yield increased progeny in infections of cell monolayers. From the number of variant sequences it can be estimated that each infectious RNA in the population differs in two to eight mutations from the average parental sequence. Thus, passaged FMDV populations consist of a pool of variants, an observation previously made with phage Q beta (E. Domingo, D. Sabo, T. Taniguchi, and C. Weissmann, Cell 13, 735-744, 1978). The FMDV genome must be described as a fluctuating distribution of sequences due to its high mutability. This may be the basis of the extensive genetic and antigenic diversity of this virus in nature.