Identification of Genotypes of Hepatitis C Virus by Sequence Comparisons in the Core, E1 and NS-5 Regions

Abstract

Isolates of hepatitis C virus (HCV) show considerable nucleotide sequence variability throughout the genome. Comparisons of complete genome sequences have been used as the basis of classification of HCV into a number of genotypes that show 67 to 77 % sequence similarity. In order to investigate whether sequence relationships between genotypes are equivalent in different regions of the genome, we have carried out formal sequence analysis of variants in the 5' non-coding region (5'NCR) and in the genes encoding the core protein, an envelope protein (El) and a non-structural protein (NS-5). In the E1 region, variants grouped into a series of six major genotypes and a series of subtypes that could be matched to the phylogenetic groupings previously observed for the NS-5 region. Furthermore, core and E1 sequences showed three non-overlapping ranges of sequence similarity corresponding to those between different genotypes, subtypes and isolates previously described in NS-5. Each major genotype could also be reliably identified by sequence comparisons in the well conserved 5'NCR, although many subtypes, such as la/lb, 2a/2c and some of those of type 4, could not be reliably distinguished from each other in this region. These data indicate that subgenomic regions such as E1 and NS-5 contain sufficient phylogenetic information for the identification of each of the 11 or 12 known types and subtypes of HCV. No evidence was found for variants of HCV that had sequences of one genotype in the 5'NCR but of a different one in the E1 or NS-5 region. This suggests that recombination between different HCV types is rare or non-existent and does not currently pose a problem in the use of subgenomic regions in classification.

Geographic distribution of hepatitis C virus genotypes in Brazil

“…Genetic variants of HCV are known to be widely spread around the world. Genotypes 1, 2 and 3 are found on all continents, but in some geographical areas, such as Africa and Southeast Asia, viral isolates are highly divergent and particular genotypes or subtypes are predominant (13)(14)(15)(16). These data suggest the existence of a long-term endemic infection in these areas and some investigators have hypothesized that HCV might have originated in such places (17).…”

Three different GB virus C/hepatitis G virus genotypes

“…First, this classification needs to be confirmed by studying other parts of the viral genome. Studies on HCV genetic heterogeneity have shown that nearly all HCV isolates segregated together in the same phylogenetic branch [14,15] for all genomic regions studied so far (5'-UTR, core, El, and NS5). To be scientifically certain, we believe that a similar approach, i.e., to confirm this phylogenetic relationship with other genomic regions, is important for definitive conclusions.…”

Evidence of intratypic recombination in natural populations of hepatitis C virus

“…Tolou et al, 2001;Uzcategui et al, 2001;, hepaciviruses (GB virus C/hepatitis G virus) (Worobey & Holmes, 2001) and Japanese encephalitis or St Louis encephalitis virus (Twiddy & Holmes, 2003). There have been few reports on recombination between HCV strains of different genotypes (Kalinina et al, 2002;Yun et al, 1996) and it has been suggested that these events are rare in vivo and that the resultant recombinants are usually not viable (Simmonds et al, 1994;Smith & Simmonds, 1997).…”