The dynamic changes of HBV quasispecies diversity in infancy after immunoprophylaxis failure: a prospective cohort study.

The dynamic changes of HBV quasispecies diversity in infancy after immunoprophylaxis failure: a prospective cohort study.
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DOI:
10.1186/s12985-021-01707-9
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发表时间:
2021-11-29
期刊:
影响因子:
4.8
通讯作者:
Li J
Li J
中科院分区:
医学3区
文献类型:
--
作者:
Li Y;Xiao Y;Li L;Song Y;Zhai X;Liu J;Duan Z;Yan L;Ding F;Liu J;Zhu L;Jiang J;Zou H;Li L;Liang C;Wang J;Li J

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先前的研究观察到,患有慢性乙型肝炎病毒(HBV)感染的年幼婴儿对抗病毒治疗的反应更敏感。然而,其根本机制仍不清楚。本研究对免疫预防失败婴儿体内乙型肝炎准种的动态变化进行了研究,为婴儿抗病毒治疗的临床管理提供病毒学解释。从前瞻性队列中招募了 13 名免疫预防失败的 7 个月大婴儿及其母亲,其中 8 名被随访至 3 岁。通过全长基因组克隆测序对乙肝准种进行了序列分析,并在不同年龄的母亲及其婴儿之间进行了比较。结果显示,7月龄婴儿的HBV准种的复杂性、突变频率和遗传距离在核苷酸水平上与母亲相比,在HBV基因组全长、部分开放阅读框和调控区方面显着下降,而当婴儿长到3岁时,则显着增加至接近母亲水平。此外,在HBV基因组的Core、PreS2、RT和P区氨基酸水平上也发现了类似的变化,特别是RT区潜在的NAs抗性突变体和Core和PreS2区的免疫逃逸突变体。这项研究揭示了母婴传播后婴儿期乙型肝炎准种的演变,这可能为解释年龄较小的儿童对抗病毒治疗更敏感提供病毒学证据。在线版本包含可在 10.1186/s12985-021-01707-9 获取的补充材料。
Previous works have observed that younger infants with chronic hepatitis B virus (HBV) infection are more responsive to antiviral treatment. However, the underlying mechanism remains unclear. In this study, the dynamic changes of HBV quasispecies in infants with immunoprophylaxis failure were investigated to provide virological explanations for clinical management on infantile antiviral therapy. Thirteen 7-month-old infants with immunoprophylaxis failure and their mothers were enrolled from a prospective cohort, and 8 of them were followed up to 3 years old. The sequences of HBV quasispecies were analyzed by the full-length genome clone-based sequencing, and compared among mothers and their infants at different ages. The results revealed that the complexity, mutation frequency and genetic distance of HBV quasispecies decreased significantly at full-length, partial open reading frames and regulatory regions of HBV genome at nucleotide level in 7-month-old infants comparing with their mothers, whereas increased significantly to near the maternal level when infants grew up to 3 years old. Furthermore, similar changes were also found in Core, PreS2, RT and P regions of HBV genome at amino acid level, especially for potential NAs-resistant mutants in RT region and immune-escape mutants in Core and PreS2 regions. This study uncovered the evolution of HBV quasispecies in infancy after mother-to-child transmission, which may provide the virological evidence for explaning that younger children are more responsive to antiviral therapy. The online version contains supplementary material available at 10.1186/s12985-021-01707-9.
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