Phylogenetic analysis of the 5' non-coding region of HCV identified a new virus type (type 4), widespread in Africa, and revealed that sequence variability is constrained by secondary RNA structures.
Identifies a new HCV genotype (type 4) and demonstrates that 5' NCR sequence variability is constrained by RNA secondary structure, enabling a rapid restriction enzyme cleavage method for virus typing.
We have analysed the pattern of nucleotide sequence variability in the 5' non-coding region (5' NCR) of geographically dispersed variants of hepatitis C virus (HCV). Phylogenetic analysis of sequences in this region indicated the existence of a new virus type, provisionally termed type 4, the identity of which was confirmed by further analysis of the more variable part of the HCV core protein coding region. The geographical distribution of HCV type 4 was distinct from that of other HCV types, it being particularly widespread in Africa and absent or rare in Europe and the Far East. Much of the variability in the 5' NCR appears to be constrained by a requirement for specific secondary structures in the viral RNA. In one of the most variable regions of the 5' NCR (positions -169 to -114), most of the nucleotide changes that are characteristic of different HCV types were covariant, with complementary substitutions at other positions. According to the proposed secondary structure of the 5' NCR, such changes preserved base pairing within a stem-loop structure, whereas the nucleotide insertions found in a proportion of 5' NCR sequences, including those of type 4, localized exclusively to the non-base-paired terminal loop. The specific nucleotide substitutions in the 5' NCR that differentiate each of the four HCV types can be detected by restriction enzyme cleavage, providing a rapid and reliable method for virus typing.
Simmonds et al. (Thu,) conducted a other in Hepatitis C virus. Sequence variability analysis of the 5' non-coding region was evaluated on Identification of HCV types and secondary structure constraints. Phylogenetic analysis of the 5' non-coding region of HCV identified a new virus type (type 4), widespread in Africa, and revealed that sequence variability is constrained by secondary RNA structures.