HBx 128-133 Deletion Affecting HBV Mother-to-Child Transmission Weakens HBV Replication via Reducing HBx Level and CP/ENII Transcriptional Activity.
HBx 128-133 Deletion Affecting HBV Mother-to-Child Transmission Weakens HBV Replication via Reducing HBx Level and CP/ENII Transcriptional Activity.
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DOI：
10.3390/v14091887
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发表时间：
2022-08-26
期刊：
影响因子：
--
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Song Y;Lu Y;Li Y;Liu M;Zhuang H;Li J;Wang J
部分B型肝炎表面抗原（HBsAg）阳性母亲所生婴儿，尤其是B e抗原（HBeAg）阳性母亲所生婴儿，仍可通过HBV母婴传播（MTCT）感染B型肝炎病毒（HBV），发展为慢性HBV感染。目前，影响乙型肝炎母婴传播的病毒学因素尚不清楚。本研究发现HBV X区氨基酸突变率高，HBeAg阳性母亲免疫预防成功组与免疫预防失败组之间有明显差异。免疫预防成功组HBx 128-133缺失（x128- 133 del）或相应的核苷酸1755-1772缺失（nt 1755 - 1772 del）突变率显著高于免疫预防失败组。此外，我们发现x128- 133 del可以通过降低HBx蛋白的水平来减弱HBV复制，这是由于增加了HBx蛋白的蛋白酶体依赖性降解，以及由于减弱了肝细胞核因子4α（HNF 4 α）与HBV CP/ENII的结合能力而降低了HBV核心启动子（CP）/增强子II（ENII）的转录活性。本研究提示x128- 133 del可能有助于免疫预防的成功，这可能有助于阐明影响HBV MTCT的病毒学机制，并为HBeAg阳性母亲所生儿童制定最佳免疫策略。
Some infants born to hepatitis B surface antigen (HBsAg)-positive mothers, especially born to hepatitis B e antigen (HBeAg)-positive mothers, can still be infected with hepatitis B virus (HBV) through mother-to-child transmission (MTCT) of HBV and develop chronic HBV infection. At present, the virological factors affecting HBV MTCT are still unclear. In this study, we found that the mutation rates of amino acids in the HBV X region were high, and there were obvious differences between the immunoprophylaxis success group and the immunoprophylaxis failure group of HBeAg-positive mothers. Specifically, the mutation rate of HBx 128–133 deletion (x128–133del) or corresponding nucleotide 1755–1772 deletion (nt1755–1772del) in the immunoprophylaxis success group was significantly higher than that in the immunoprophylaxis failure group. Furthermore, we found that x128–133del could weaken HBV replication by reducing the level of the HBx protein due to the increased proteasome-dependent degradation of HBx protein, and the transcriptional activity of HBV core promoter (CP)/enhancer II (ENII) due to the attenuated binding capacity of hepatocyte nuclear factor 4α (HNF4α) to HBV CP/ENII. This study suggests that x128–133del may contribute to immunoprophylaxis success, which may be helpful in clarifying the virological mechanism affecting HBV MTCT and formulating an optimal immunization strategy for children born to HBeAg-positive mothers.
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影响因子：
4.8
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
通讯作者：
Li J
影响因子：
12.7
作者：
Huang, Yong;Wang, Bo;Chen, Weixian
通讯作者：
Chen, Weixian
性别决定区 Y 盒 4 (SOX4) 通过抑制肝细胞核因子 4 α 表达来抑制乙型肝炎病毒复制
影响因子：
7.6
作者：
Shi, Shu;Liu, Mingchen;Lu, Fengmin
通讯作者：
Lu, Fengmin
免疫预防失败婴儿乙型肝炎病毒准种特征
DOI：
10.1007/s10096-018-3235-5
发表时间：
2018-06-01
影响因子：
4.5
作者：
Wang, Xin;Deng, Wanyan;Long, Quanxin
通讯作者：
Long, Quanxin
影响因子：
25.7
作者：
Lucifora, Julie;Arzberger, Silke;Protzer, Ulrike
通讯作者：
Protzer, Ulrike