中国甲型肝炎病毒分离株全基因组特征及准种分布

Hao Wang, Xinying Wang, Jingyuan Cao, Yan Gao, Wenting Zhou, Shengli Bi
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引用次数: 3

摘要

甲型肝炎病毒(HAV)感染是急性病毒性肝炎的最常见原因,对全世界的公共卫生具有重大影响。为了确定在中国流行的甲型肝炎毒株的特征,对2006-2009年在不同省份收集的5份样本进行了完全测序。基于不同片段的系统发育分析表明,5个序列均属于IA亚基因型,但部分片段存在细微差异。在已知的中和表位位点上没有发现氨基酸突变,在免疫优势位点附近发现了一个独特的取代。虽然没有检测到异型间重组,但在研究中发现了异型内重组信号。分子进化分析表明,全球基因型I的平均替换率为3.27 × 10−4个替换/位点/年,与最近共同祖先(tMRCA)的时间约为267年。结果表明,突变频率高的区域主要集中在非结构蛋白编码序列。本研究对中国HAV毒株的基因型分布、选择压力、中和表位突变、重组事件和准种分布等方面进行了研究。分析了甲型肝炎I基因型在世界范围内的进化状况,为进一步开展甲型肝炎分子流行病学研究提供参考。
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Full-length genome characterization and quasispecies distribution of hepatitis A virus isolates in China

Hepatitis A virus (HAV) infection is the most common cause of acute viral hepatitis and has significant implications to public health worldwide. To characterize HAV strains circulating in China, five samples collected in different provinces from 2006–2009 were entirely sequenced. Phylogenetic analysis based on distinct segments showed that all five sequences belonged to subgenotype IA, but with slight differences in some fragments. No amino acid mutations were found at the known neutralizing epitope sites, and one unique substitution was identified near the immunodominant site. While no intertypic recombination was detected, intratypic recombination signals were found in the study. Molecular evolution analyses showed that the estimated mean substitution rate of genotype I worldwide was 3.27 × 10 4 substitutions/site/year, and the time to the most recent common ancestor (tMRCA) was about 267 years ago. The quasispecies distribution across the complete genome was also evaluated, and the high mutation frequency regions were mainly at the nonstructural protein coding sequences. This study contributed information on the genotype distribution, selection pressure, neutralizing epitope site mutations, recombination events and quasispecies distribution of HAV strains in China. The evolutionary status of genotype I worldwide was also analyzed, which will provide a reference for future HAV molecular epidemiology studies.

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