Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100083, P.R. China.
Department of Clinical Laboratory, Peking University First Hospital, Beijing, 100034, P.R. China.
Gut. 2020 May;69(5):933-941. doi: 10.1136/gutjnl-2019-318278. Epub 2019 Aug 24.
This study was performed to explore the correlation between the characteristics of hepatitis B virus (HBV) quasispecies in HBV-infected pregnant women and the risk of immunoprophylaxis failure for their infants.
In this prospective nested case-control study, the characteristics of HBV quasispecies in mothers whose infants were immunoprophylaxis success (control group) and those whose infants were immunoprophylaxis failure (case group) were analysed by the clone-based sequencing of full-length HBV genome and next-generation sequencing (NGS) of "a" determinant region, and were compared between the two groups.
The quasispecies characteristics including mutant frequency, Shannon entropy and mean genetic distance at amino acid level of "a" determinant region were significantly lower in case group than that in control group, using the full-length HBV genome clone-based sequencing assay. These results were confirmed by NGS assay. Notably, we discovered that the differences were also significant at nucleotide level by NGS assay. Furthermore, the risk of immunoprophylaxis failure could be predicted by analysing the three HBV quasispecies characteristics either at nucleotide level or at amino acid level of "a" determinant region, and the corresponding predictive values were tentatively set up.
HBV quasispecies with a more complex mutant spectrum in "a" determinant region might be more vulnerable to extinct through mother-to-child-transmission (MTCT). More importantly, analysing HBV quasispecies characteristics in pregnant women with high HBV DNA load might be helpful to predict the high-risk population of immunoprophylaxis failure, and consequently provide accurate intervention against MTCT of HBV.
本研究旨在探讨乙型肝炎病毒(HBV)感染孕妇病毒准种特征与婴儿免疫预防失败风险之间的相关性。
在这项前瞻性巢式病例对照研究中,通过克隆测序全长 HBV 基因组和下一代测序(NGS)分析“a”决定区,分析免疫预防成功(对照组)和免疫预防失败(病例组)婴儿母亲的 HBV 准种特征,并比较两组之间的特征。
使用全长 HBV 基因组克隆测序检测,病例组“a”决定区的突变频率、香农熵和氨基酸水平平均遗传距离等准种特征明显低于对照组。NGS 检测也证实了这一结果。值得注意的是,我们发现 NGS 检测还显示核苷酸水平也存在显著差异。此外,通过分析“a”决定区核苷酸或氨基酸水平的三种 HBV 准种特征,也可以预测免疫预防失败的风险,并且初步建立了相应的预测值。
“a”决定区具有更复杂突变谱的 HBV 准种可能更容易通过母婴传播(MTCT)而消失。更重要的是,分析高 HBV DNA 载量孕妇的 HBV 准种特征可能有助于预测免疫预防失败的高危人群,从而为 HBV 的 MTCT 提供准确的干预措施。