Quasispecies characteristics in mother-to-child transmission of hepatitis B virus by next-generation sequencing
Quasispecies characteristics in mother-to-child transmission of hepatitis B virus by next-generation sequencing
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DOI：
10.1016/j.jinf.2017.04.012
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发表时间：
2017-07-01
影响因子：
28.2
通讯作者：
Wang, Zhanhui
中科院分区：
文献类型：
--
作者：
Yang, Guifeng;Liu, Zhihua;Wang, Zhanhui
目的：了解母婴传播(MTCT)母婴传播的乙型肝炎病毒(HBVDNA)在宿主内的准种特征。方法：采用下一代测序(NGS)技术，对37对母婴传播的HBVPre-C/C基因进行序列分析。结果：系统发育分析和荧光分析表明，母婴传播中可能同时存在单个株和多个不同株的传播。然而，对重组病毒序列的分析显示，变异在儿童中的分布相对较窄，这一点在儿童中的病毒多样性低于母亲中得到证实。在七名ALT水平升高的儿童中，观察到了具有两到五个高频突变组合的密切相关的新变种；新变种超过了传播的母体变种，成为其中五个变种的主导菌株。此外，这些儿童存在30个突变，频率为宿主内所有病毒的1%；这些突变导致19个氨基酸替换。有趣的是，几乎所有的改变都位于众所周知的T细胞或B细胞表位内。结论：通过MTCT在慢性乙肝感染的早期阶段发生了限制性改变，其临床后果各不相同。这些数据可能对未来相关免疫发病机制和治疗策略的研究具有重要意义。(C)2017年英国感染协会。爱思唯尔有限公司出版。保留所有权利。
Objectives: To identify within-host quasispecies characteristics of hepatitis B virus (HBV) in mothers and children infected via mother-to-child transmission (MTCT).Methods: Using next-generation sequencing (NGS), we analyzed sequences within the non-overlapping pre-core/core (pre-C/C) gene in 37 mother-child pairs.Results: Phylogenetic and Highlighter analyses suggested that both a single strain and multiple distinct strains may be transmitted in MTCT of HBV. However, analysis of reassembled viral sequences revealed a relatively narrow distribution of variants in children, which was confirmed by a lower viral diversity in children than that in mothers. New closely related variants with combinations of two to five high-frequency mutations were observed in seven children with elevated ALT levels; the new variants out-competed the transmitted maternal variants to become the dominant strains in five of them. Furthermore, 30 mutations with a frequency > 1% of all viruses within-host were present in those children; the mutations caused 19 amino-acid substitutions. Interestingly, almost all were located within the well-known T-cell or B-cell epitopes.Conclusions: There are restrictive changes that occur in the early stages of chronic HBV infection through MTCT with different clinical consequences. These data might have important implications for future investigations of interrelated immunopathogenesis and therapeutic strategies. (C) 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.