Conservation in China of a novel group of HCV variants dating to six centuries ago

Abstract

We characterized a novel group of HCV variants that are genetically related but distinct from each other belonging to genotype 6 (HCV-6). From 26 infected Austronesian-descended aborigines on Hainan Island, China, HCV sequences were determined followed by genetic analyses. Six nearly full-length genomes and 20 E1 sequences of HCV were obtained, which differ from each other and from all known HCV lineages by nucleotides above the intra-subtype level of 13%. Together with subtypes 6g and 6w, they constitute a phylogenetic group sharing a common ancestor dating from the end of the 12th century.

Conclusion: Our data indicate the maintenance of an isolated HCV-6 indigenous circulation on Hainan Island at least for six centuries.

Keywords: Austronesian aborigines; China; Evolution; HCV genotype 6; Hainan Island.

Figure 1

ML trees estimated based on (A) nearly full-length genome, (B) partial NS5B sequences corresponding to nucleotides 8316–8620 in the reference H77 genome, and (C) the sequences in E1 region corresponding to nucleotides 674–1085. With the exception of the six HK-genomes (red branches) and 20 HNLZ-variants (green branches) determined in this study, references from subtype 6a–6xa and many unclassified variants of HCV-6 (uncl) are also included. In tree (A) the reference H77 genome (GenBank accession number: NC_004102) is used as an outlier group. In both trees (A) and (C), each branch leads to an isolate ID, in which the unclassified variants are each labelled with a prefix 6_before the ID, while in the tree (B), the isolates are shown in the following format: genotype or subtype.country of isolation.isolate ID or GenBank accession number. To allow the isolates to be readily distinguished, assigned subtypes (6a–6xa) and unclassified lineages (uncl) are indicated above the related branches (A) or on the right side with half brackets (B and C). Bootstrap supports are indicated in italics. The scale bars represent 0.10 nucleotide substitutions per site.

Figure 2

Time-scaled phylogenetic trees estimated based on the sequences in core, E1, and NS5B regions, corresponding to the nucleotides numbered 342–915, 891–1302, and 7602–9308 in the H77 genome, respectively. In each tree, the branch lengths represent the evolutionary time as measured by the grids corresponding to a reverse timescale at the tree base, from the present (right) to the past (left) and a time point indicated by a green circle marks the time (along with its 95% HDP) at which the related lineage had diverged. The six HK genomes are indicated by red branches while the 20 HNLZ sequences are denoted by pink branches. For simplicity, only those posterior scores related to the Hainan variants are shown above the internal nodes.