Figure 1.

Known RNA secondary structures in the downstream NS5B coding region including the cis-replication element (CRE, 5BSL3.2) which are relevant for replication control. (A) RNA secondary structures are colored by the number of base pair types illustrating the extent of covariations in double-stranded regions. The SL IV (or 5BSL3.4) contains the NS5B stop codon in the apical loop. The structure was visualized using R2DT⁵⁹. The nucleotide sequence shows the most informative sequence (IUPAC code) calculated by RNAalifold⁶⁰ based on the alignment. Lowercase letters indicate gaps in the alignment column. (B) RNA secondary structure dot-bracket annotation (SS), structure consensus (StrucC), sequence consensus (SeqC), and the fraction of nucleotides used from synonymous codons (SynCo). Thereby, a low value indicates that only a few nucleotide(s) out of all nucleotides possible for synonymous codons are actually used by the different HCV isolates, indicating a high degree of primary sequence conservation which goes beyond the requirements of the coding sequence. This provides evidence that a conserved functional RNA element may overlap with the coding sequence. Alignments shown in Figs. S12 and S13.