TABLE 1

Mutant spectrum analysis by molecular cloning and Sanger sequencing of the glycoprotein Gc-coding region of RVFV passaged 4 times in Vero cells

RVFV populationaNo. of nucleotides analyzed (clones/haplotypes)bNo. different (total) mutationscMinimum mutation frequencydMaximum mutation frequencyeNo. different synonymous (nonsynonymous) mutationsTotal no. synonymous (nonsynonymous) mutations
56/74 p4, no drug31,610 (29/21)53 (375)1.7 × 10−31.2 × 10−248 (5)354 (21)
56/74 p4 + favipiravir31,610 (29/29)138 (348)4.4 × 10−31.1 × 10−285 (53)284 (64)
  • a The origin and passage history of the viral populations analyzed is described in Fig. 2 and in Materials and Methods.

  • b The genomic region analyzed spans residues 2110 to 3199 of the glycoprotein Gc-coding region; the residue numbering is that of the SA-75 genome. The values in parenthesis indicate the number of clones analyzed followed by the number of haplotypes (number of different RNA sequences).

  • c The number of different and total mutations were counted relative to the consensus sequence of the corresponding population. Different and total mutations were used to calculate the minimum and maximum mutation frequency, respectively.

  • d Data represent the average number of different mutations per nucleotide in the mutant spectrum relative to the consensus sequence of the corresponding population. The results indicate a significant 2.5-fold increase of minimum mutation frequency associated with replication in the presence of favipiravir (P < 0.0001; χ2 test).

  • e Data represent the average number of total mutations per nucleotide in the mutant spectrum relative to the consensus sequence of the corresponding population.