C2729T mutation associated with HBV mother-to-child transmission reduces HBV production via suppressing LHBs expression.
C2729T mutation associated with HBV mother-to-child transmission reduces HBV production via suppressing LHBs expression.
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DOI：
10.1080/21505594.2023.2189676
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发表时间：
2023-12
期刊：
影响因子：
5.2
通讯作者：
Wang, Jie
中科院分区：
文献类型：
--
作者：
Liu, Minmin;Song, Yarong;Li, Yi;Yang, Xingwen;Zhuang, Hui;Li, Jie;Wang, Jie
关键词：
母婴传播（MTCT）仍然是乙型肝炎病毒（HBV）感染的主要途径。然而，影响HBV母婴传播的病毒学因素尚未完全阐明。在这项研究中，基于母体乙型肝炎表面抗原（HBsAg）阳性母婴对的前瞻性队列，我们发现免疫预防成功组中HBV preS1启动子（SPI）区的平均核苷酸突变率显着高于免疫预防失败组。 HBV SPI区的核苷酸突变中，C2729T突变频率最高。接下来，我们发现C2729T突变通过抑制大乙型肝炎表面抗原（LHBs）的表达促进HBsAg释放，但减少HBV产生，而过度表达LHBs可以挽救这种现象。基于C2729T突变可以改变HBV SPI区域中肝细胞核因子1（HNF1）的结合位点这一事实，我们发现这种改变可以通过减弱HNF1与HBV SPI区域的结合能力来下调SPI的转录活性。这项研究表明，HBV C2729T 突变可能通过减少 HBV 产生来补充影响 HBV MTCT 的病毒学因素，从而有助于 HBV MTCT 免疫预防的成功。
Mother-to-child transmission (MTCT) is still the main route of hepatitis B virus (HBV) infection. However, the virological factors affecting HBV MTCT have not been fully elucidated. In this study, based on a prospective cohort of mother-infant pairs with positive maternal hepatitis B surface antigen (HBsAg), we found that the average nucleotide mutation rate of HBV preS1 promoter (SPI) region in the immunoprophylaxis success group was significantly higher than that in the immunoprophylaxis failure group. Among the nucleotide mutations of the HBV SPI region, the C2729T mutation had the highest frequency. Next, we found that the C2729T mutation promoted HBsAg release but reduced HBV production by suppressing the expression of large hepatitis B surface antigen (LHBs), and overexpressing LHBs could rescue this phenomenon. Based on the fact that the C2729T mutation could alter the binding site of hepatocyte nuclear factor 1 (HNF1) in the HBV SPI region, we uncovered that such an alteration could downregulate the transcriptional activity of SPI by attenuating the binding ability of HNF1 and HBV SPI region. This study suggests that HBV C2729T mutation may contribute to the immunoprophylaxis success of HBV MTCT by reducing HBV production, which supplements the virological factors affecting HBV MTCT.
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影响因子：
12.7
作者：
Huang, Yong;Wang, Bo;Chen, Weixian
通讯作者：
Chen, Weixian
DOI：
10.3390/v14091887
发表时间：
2022-08-26
期刊：
Viruses
影响因子：
--
作者：
Song Y;Lu Y;Li Y;Liu M;Zhuang H;Li J;Wang J
通讯作者：
Wang J
影响因子：
3.7
作者：
NISHIZONO, A;MAENO, M;SHIKATA, T
通讯作者：
SHIKATA, T
影响因子：
5.6
作者：
Tan, WS;Dyson, MR;Murray, K
通讯作者：
Murray, K
影响因子：
25.7
作者：
FERNHOLZ, D;STEMLER, M;WILL, H
通讯作者：
WILL, H