Abstract
BackgroundHepatitis C virus (HCV) has been the subject of intense research and clinical investigation as its major role in human disease has emerged. Previous and recent studies have suggested a diversification of type 1 HCV in the South American region. The degree of genetic variation among HCV strains circulating in Bolivia and Colombia is currently unknown. In order to get insight into these matters, we performed a phylogenetic analysis of HCV 5' non-coding region (5'NCR) sequences from strains isolated in Bolivia, Colombia and Uruguay, as well as available comparable sequences of HCV strains isolated in South America.MethodsPhylogenetic tree analysis was performed using the neighbor-joining method under a matrix of genetic distances established under the Kimura-two parameter model. Signature pattern analysis, which identifies particular sites in nucleic acid alignments of variable sequences that are distinctly representative relative to a background set, was performed using the method of Korber & Myers, as implemented in the VESPA program. Prediction of RNA secondary structures was done by the method of Zuker & Turner, as implemented in the mfold program.ResultsPhylogenetic tree analysis of HCV strains isolated in the South American region revealed the presence of a distinct genetic lineage inside genotype 1. Signature pattern analysis revealed that the presence of this lineage is consistent with the presence of a sequence signature in the 5'NCR of HCV strains isolated in South America. Comparisons of these results with the ones found for Europe or North America revealed that this sequence signature is characteristic of the South American region.ConclusionPhylogentic analysis revealed the presence of a sequence signature in the 5'NCR of type 1 HCV strains isolated in South America. This signature is frequent enough in type 1 HCV populations circulating South America to be detected in a phylogenetic tree analysis as a distinct type 1 sub-population. The coexistence of distinct type 1 HCV subpopulations is consistent with quasispecies dynamics, and suggests that multiple coexisting subpopulations may allow the virus to adapt to its human host populations.
Highlights
Hepatitis C virus (HCV) has been the subject of intense research and clinical investigation as its major role in human disease has emerged
Phylogentic analysis revealed the presence of a sequence signature in the 5' noncoding region (5'NCR) of type 1 HCV strains isolated in South America
This signature is frequent enough in type 1 HCV populations circulating South America to be detected in a phylogenetic tree analysis as a distinct type 1 sub-population
Summary
Hepatitis C virus (HCV) has been the subject of intense research and clinical investigation as its major role in human disease has emerged. In order to get insight into these matters, we performed a phylogenetic analysis of HCV 5' noncoding region (5'NCR) sequences from strains isolated in Bolivia, Colombia and Uruguay, as well as available comparable sequences of HCV strains isolated in South America. Most of the genome forms a single open reading frame (ORF) that encodes three structural (core, E1, E2) and seven non-structural (p7, NS2-NS5B) proteins. Short untranslated regions at each end of the genome (5'NCR and 3'NCR) are required for replication of the genome. This process requires a cis-acting replication element in the coding sequence of NS5B recently described [5]. Translation of the single ORF is dependent on an internal ribosomal entry site (IRES) in the 5'NCR, which interacts directly with the 40S ribosomal subunit during translation initiation [6]
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