组蛋白去乙酰化酶和乙酰​​化组蛋白H3参与乙型肝炎病毒DNA

StephenW

Life Sci. 2019 Mar 9. pii: S0024-3205(19)30166-3. doi: 10.1016/j.lfs.2019.03.010. [Epub ahead of print]
Histone deacetylases and acetylated histone H3 are involved in the process of hepatitis B virus DNA replication.
Zhang D1, Wang Y1, Zhang HY1, Jiao FZ1, Zhang WB1, Wang LW1, Zhang H2, Gong ZJ3.
Author information

1
    Department of Infectious Diseases, Renmin Hospital of Wuhan University, 430060 Wuhan, China.
2
    Department of Pharmaceutical, Renmin Hospital of Wuhan University, 430060 Wuhan, China.
3
    Department of Infectious Diseases, Renmin Hospital of Wuhan University, 430060 Wuhan, China. Electronic address: [email protected].

Abstract
AIMS:

The aim of this study was to investigate the relationship between anti-HBV treatment and the regulation of HDACs during HBV DNA replication.
METHODS:

HDAC activities and HBV DNA levels in CHB patients' sera were measured and correlation analysis was made. The changes of HDAC2, HDAC6, AH3 and histone H3 levels in normal control and 4 CHB patient liver tissue samples before and after antiviral treatment were examined. The HDAC inhibitor, TSA, anti-HBV agents, ETV and IFN-α were used to stimulate HepG2.2.15 cells. The levels of HBV DNA, pgRNA in supernatants, and cccDNA in the cells were determined by PCR. The HDAC activity, HDAC6, HDAC2, AH3 and H3 protein levels in cells were tested at days 3, 6, and 9 after treatments.
KEY FINDINGS:

HDAC activity was positively correlated with HBV DNA in the HBV patients' sera. The levels of HDAC2, HDAC6 and AH3 were notably decreased after antiviral treatment. When compared with antiviral treatment group, the normal liver tissue showed obviously decreased HDAC2, HDAC6 and AH3 protein levels. In vitro study, the level of HBV DNA, the HDAC activity, and the HDAC2, HDAC6 and AH3 protein levels decreased in the ETV, IFN-α and TSA groups compared with the control group. The pgRNA level in supernatants was declined in the IFN-α group and increased in the ETV and TSA groups. cccDNA expression was suppressed by IFN-α.
SIGNIFICANCE:

The changes of HBV replicative products during antiviral treatment are associated with histone deacetylation. Acetylated histone H3 is involved in the process of hepatitis B virus DNA replication.

Copyright © 2018. Published by Elsevier Inc.
KEYWORDS:

Acetylated histone H3; HBV DNA; Histone deacetylases; Replication

PMID:
    30862568
DOI:
    10.1016/j.lfs.2019.03.010

StephenW

生命科学。 2019年3月9日.pii：S0024-3205（19）30166-3。 doi：10.1016 / j.lfs.2019.03.010。 [印刷前的电子版]
组蛋白去乙酰化酶和乙酰​​化组蛋白H3参与乙型肝炎病毒DNA复制过程。
Zhang D1，Wang Y1，Zhang HY1，Jiao FZ1，Zhang WB1，Wang LW1，Zhang H2，Gong ZJ3。
作者信息

1
    武汉大学人民医院感染科，武汉430060
2
    武汉大学人民医院药学系，武汉430060
3
    武汉大学人民医院感染科，武汉430060电子地址：[email protected]。

抽象
目的：

本研究的目的是研究抗HBV治疗与HBV DNA复制过程中HDACs调节之间的关系。
方法：

测定CHB患者血清中HDAC活性和HBV DNA水平，并进行相关分析。检测了抗病毒治疗前后正常对照组和4例CHB患者肝组织中HDAC2，HDAC6，AH3和组蛋白H3水平的变化。 HDAC抑制剂，TSA，抗HBV药物，ETV和IFN-α用于刺激HepG2.2.15细胞。通过PCR测定HBV DNA，上清液中的pgRNA和细胞中的cccDNA的水平。在处理后第3,6和9天测试细胞中的HDAC活性，HDAC6，HDAC2，AH3和H3蛋白水平。
主要发现：

HDV活性与HBV患者血清中的HBV DNA呈正相关。抗病毒治疗后HDAC2，HDAC6和AH3的水平显着降低。与抗病毒治疗组相比，正常肝组织中HDAC2，HDAC6和AH3蛋白水平明显降低。在体外研究中，与对照组相比，ETV，IFN-α和TSA组中HBV DNA水平，HDAC活性以及HDAC2，HDAC6和AH3蛋白水平降低。上清液中的pgRNA水平在IFN-α组中下降并且在ETV和TSA组中增加。 IFN-α抑制cccDNA表达。
意义：

抗病毒治疗期间HBV复制产物的变化与组蛋白去乙酰化有关。乙酰化组蛋白H3参与乙型肝炎病毒DNA复制过程。

版权所有©2018。由Elsevier Inc.出版
关键词：

乙酰化组蛋白H3; HBV DNA;组蛋白去乙酰化酶;复制

结论：
    30862568
DOI：
    10.1016 / j.lfs.2019.03.010