HBx 128–133 缺失影響 HBV 母嬰傳播通過降低 HBx 水平和 CP/ENII

StephenW

HBx 128–133 缺失影響 HBV 母嬰傳播通過降低 HBx 水平和 CP/ENII 轉錄活性削弱 HBV 複製
作者：宋雅容
1,2、瀛路
1、伊莉
1、劉敏敏
1、惠莊
1、傑麗
1、*和王杰
1,2,* [獸人]
1
北京大學醫學部基礎醫學院微生物與傳染病中心, 北京 100191
2
NHC醫學免疫學重點實驗室/北京大學免疫學研究平台, 北京 100191
*
應向其通信的作者。
學術編輯：Mark W. Douglas 和 Thomas Tu
病毒 2022, 14(9), 1887; https://doi.org/10.3390/v14091887
收到日期：2022 年 8 月 15 日 / 接受日期：2022 年 8 月 24 日 / 發布日期：2022 年 8 月 26 日
（這篇文章屬於特刊 乙型肝炎病毒：征服古老疾病的新突破）
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抽象的
一些乙型肝炎表面抗原（HBsAg）陽性母親所生的嬰兒，尤其是乙型肝炎e抗原（HBeAg）陽性母親所生的嬰兒，仍然可以通過母嬰傳播（MTCT）感染乙型肝炎病毒（HBV） HBV 和發展為慢性 HBV 感染。目前，影響HBV母嬰傳播的病毒學因素仍不清楚。本研究發現HBV X區氨基酸突變率較高，且HBeAg陽性母親免疫預防成功組與免疫預防失敗組存在明顯差異。具體而言，免疫預防成功組HBx 128-133缺失（x128-133del）或相應核苷酸1755-1772缺失（nt1755-1772del）的突變率顯著高於免疫預防失敗組。此外，我們發現 x128-133del 可以通過降低 HBx 蛋白水平來削弱 HBV 複製，這是由於 HBx 蛋白的蛋白酶體依賴性降解增加，而 HBV 核心啟動子 (CP)/增強子 II (ENII) 的轉錄活性由於肝細胞核因子 4α (HNF4α) 與 HBV CP/ENII 的結合能力減弱。本研究表明，x128-133del 可能有助於免疫預防的成功，這可能有助於闡明影響 HBV 母嬰傳播的病毒學機制，並為 HBeAg 陽性母親所生兒童制定最佳免疫策略。查看全文
關鍵詞：乙型肝炎病毒；母嬰傳播； X區突變；乙肝病毒複製；肝細胞核因子4α

StephenW

HBx 128–133 Deletion Affecting HBV Mother-to-Child Transmission Weakens HBV Replication via Reducing HBx Level and CP/ENII Transcriptional Activity
by Yarong Song
1,2, Ying Lu
1, Yi Li
1, Minmin Liu
1, Hui Zhuang
1, Jie Li
1,* and Jie Wang
1,2,* [ORCID]
1
Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
2
NHC Key Laboratory of Medical Immunology/Immunology Research Platform of Peking University, Beijing 100191, China
*
Authors to whom correspondence should be addressed.
Academic Editors: Mark W. Douglas and Thomas Tu
Viruses 2022, 14(9), 1887; https://doi.org/10.3390/v14091887
Received: 15 August 2022 / Accepted: 24 August 2022 / Published: 26 August 2022
(This article belongs to the Special Issue Hepatitis B Virus: New Breakthroughs to Conquer an Ancient Disease)
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Abstract
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. View Full-Text
Keywords: hepatitis B virus; mother-to-child transmission; X region mutation; HBV replication; hepatocyte nuclear factor 4α

StephenW

https://www.mdpi.com/1999-4915/14/9/1887/htm