Institute of Basic and Clinical Medicine, Yunnan Provincial Key Laboratory for Clinical Virology, Key Laboratory for Birth Defects and Genetic Diseases, the First People's Hospital of Yunnan Province, Kunming, China.
Institute of Basic and Clinical Medicine, Yunnan Provincial Key Laboratory for Clinical Virology, Key Laboratory for Birth Defects and Genetic Diseases, the First People's Hospital of Yunnan Province, Kunming, China.
Virus Res. 2019 Nov;273:197762. doi: 10.1016/j.virusres.2019.197762. Epub 2019 Sep 18.
To analyze the hepatitis B virus (HBV) quasi-subgenotype B3 characters and molecular evolution in Southeast Asia, 411 serum samples with HBsAg positive were collected from Xishuangbanna, China. After DNA extraction, PCR amplification and sequencing, a total of 183 HBV full-length genomes were obtained. Phylogenetic analysis showed 139 stains (76.0%) were genotype B, 41 strains were genotype C (22.4%) and 3 strains were genotype I (1.6%). Among genotype B, 34 sequences were identified as quasi-subgenotype B3. Quasi-subgenotype B3 sequences from this study and quasi-subgenotype B3 sequences from the GenBank (total of 141 complete genome sequences) were grouped into quasi-subgenotype B3 (B3, formerly B5, Chinese B6 and B7-9). Sixteen peculiar nucleotides distributed in quasi-subgenotype B3 were identified, which were differ from B1, B2, B4 and B5(formerly B6) (nt93 T, nt100C, nt355 G, nt843 T, nt861C, nt912C, nt929 T, nt930 G, nt1023 T, nt1041 T, nt2651C, nt2693 T, nt2970C, nt3054A, nt3087A and nt3171 G). Then Evolutionary dynamics analysis of HBV quasi-subgenotype B3 was performed. The mean rate of nucleotide substitution for HBV quasi-subgenotype B3 was estimated to be around 5.556-5.660 × 10 substitutions/site/year. Estimated time to most recent ancestor of quasi-subgenotype B3 was around the 1847-1945(95%HPD), and Yunnan strains might be the parental strains. The Bayesian sky plot showed a steady spreading of HBV quasi-genotype B3 from early of 1940s to 90 s. In summary, HBV quasi-subgenotype B3 infection is prevalent in Southeast Asia based on the current reports and still with a high prevalence rate based on the evolutionary dynamics analysis. Current vaccine and nucleotide analogues might have effective prevention and treatment for HBV quasi-subgenotype B3 based on the rare clinically relevant mutation sites included in quasi-subgenotype B3.
为分析东南亚乙型肝炎病毒（HBV）准亚型 B3 的特征和分子进化，从中国西双版纳采集了 411 份 HBsAg 阳性血清样本。提取 DNA 后，进行 PCR 扩增和测序，共获得 183 株 HBV 全长基因组。系统进化分析显示 139 株（76.0%）为基因型 B，41 株为基因型 C（22.4%），3 株为基因型 I（1.6%）。在基因型 B 中，有 34 个序列被鉴定为准亚型 B3。本研究的准亚型 B3 序列和 GenBank 中的准亚型 B3 序列（共 141 个完整基因组序列）被分为准亚型 B3（B3，以前称为 B5、中国 B6 和 B7-9）。在准亚型 B3 中发现了 16 个独特的核苷酸，它们与 B1、B2、B4 和 B5（以前称为 B6）不同（nt93T、nt100C、nt355G、nt843T、nt861C、nt912C、nt929T、nt930G、nt1023T、nt1041T、nt2651C、nt2693T、nt2970C、nt3054A、nt3087A 和 nt3171G）。然后对 HBV 准亚型 B3 的进化动力学进行了分析。HBV 准亚型 B3 的核苷酸替代率估计约为 5.556-5.660×10 个替换/site/年。准亚型 B3 的最近共同祖先的估计时间约为 1847-1945 年（95%HPD），云南株可能是亲代株。贝叶斯天空图显示，HBV 准基因 B3 从 20 世纪 40 年代初到 90 年代一直在稳定传播。总之，根据目前的报告，HBV 准亚型 B3 感染在东南亚流行，根据进化动力学分析，其流行率仍然很高。基于准亚型 B3 中包含的罕见临床相关突变位点，目前的疫苗和核苷酸类似物可能对 HBV 准亚型 B3 具有有效的预防和治疗作用。
