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The Transmission Route and Selection Pressure in HCV Subtype 3a and 3b Chinese Infections: Evolutionary Kinetics and Selective Force Analysis

ABSTRACT: Hepatitis C virus (HCV) genotype 3 (GT-3) represents 22–30% of all infections and is the second most common genotype among all HCV genotypes. It has two main subtypes, GT-3a and GT-3b, that present epidemiological differences in transmission groups. This report generated 56 GT-3a and 64 GT-3b whole-genome sequences to conduct an evolutionary kinetics and selective force analysis with reference sequences from various countries. Evolutionary analysis showed that HCV GT-3a worldwide might have been transmitted from the Indian subcontinent to South Asia, Europe, North America and then become endemic in China. In China, GT-3a may have been transmitted by intravenous drug users (IDUs) and become endemic in the general population, while GT-3b may have originated from IDUs and then underwent mutual transmission between blood donors (BDs) and IDUs, ultimately becoming independently endemic in IDUs. Furthermore, the spread of GT-3a and GT-3b sequences from BD and IDU populations exhibit different selective pressures: the proportion of positively selected sites (PPSs) in E1 and E2 from IDUs was higher than in BDs. The number of positive selection sites was higher in GT-3b and IDUs. These results indicate that different selective constraints act along with the GT-3a and GT-3b genomes from IDUs and BDs. In addition, GT-3a and GT-3b have different transmission routes in China, which allows us to formulate specific HCV prevention and control strategies in China.

SUBMITTER: Xu R

PROVIDER: S-EPMC9324606 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundHCV genotype 6 (HCV-6) typically circulates in Southeast Asia and exhibits the highest genetic diversity among the eight HCV genotypes. In our previous work, a group of HCV-6 sequences was not clearly classified. Here, we further characterized this HCV-6 variant and analyzed the evolutionary history of the enlarged HCV-6 family.MethodsBlood samples from eight HCV seropositive samples collected from intravenous drug users (IDUs) in 2014 in Yunnan Province, China. The full-length HCV genome sequences were amplified by using reverse transcription PCR followed by DNA sequencing and phylogenetic analysis. Bayesian evolutionary analysis was performed with the complete coding region sequences of subtype 6a-6xh.ResultsThe eight genomes had the same coding region of 9051 nucleotides. The complete coding region sequences of the eight HCV isolates formed a distinct phylogenetic group from the previously assigned HCV-6 subtypes (6a-6xf), however which clustered with 6xg reference sequences that were found in Kachin State, Myanmar, and recently assigned and released. The p-distances of the eight isolates to subtype 6a-6xf and 6xh ranged from 0.143 to 0.283. Based on the HCV-6 complete coding region sequences, we constructed a timescaled phylogenetic tree to reveal the HCV-6 evolutionary history, in which there were four HCV-6 phylogenetic subsets, whose median tMRCAs were 294.8, 388.5, 348.5 and 197.0 years ago, respectively. Subtype 6xg clustered into Subset I, and had the most recent common ancestor with subtype 6n, which dated back to 101.2 (95% HPD: 78.7, 125.8) years ago. The genetic evolutionary analysis further confirmed that subtype 6xg originated from Myanmar, and transmitted to Dehong through cross-border IDUs.ConclusionThe HCV-6 variant characterized in this study belonged to newly assigned subtype 6xg. Our finding further confirmed the assignment of 6xg. HCV-6 family was highly divers and had a complicated evolutionary history in Southeast Asia. It is necessary to further characterize HCV-6 genetics in this region.

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The Transmission Route and Selection Pressure in HCV Subtype 3a and 3b Chinese Infections: Evolutionary Kinetics and Selective Force Analysis

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