乙型肝炎病毒的HBx和HBc可以通过降低其转录和稳定性来影响Id

StephenW

Virus Res. 2020 Apr 16:197973. doi: 10.1016/j.virusres.2020.197973. [Epub ahead of print]
The HBx and HBc of hepatitis B virus can influence Id1 and Id3 by reducing their transcription and stability.
Xia L1, Wang S2, Zhang H3, Yang Y4, Wei J4, Shi Y5, Zou C5, Liu J5, Luo M6, Huang A4, Wang D7.
Author information

1
    Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, Chongqing Medical University, Chongqing, China; College of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
2
    Department of Dermatology and Cosmetology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China.
3
    Department of Clinical Laboratory, Chongqing Health Center for Women and Children, Chongqing, China.
4
    Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, Chongqing Medical University, Chongqing, China.
5
    College of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
6
    Department of Clinical Laboratory, Yubei District People's Hospital, Chongqing, China.
7
    Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, Chongqing Medical University, Chongqing, China; College of Laboratory Medicine, Chongqing Medical University, Chongqing, China. Electronic address: [email protected].

Abstract

Hepatitis B virus (HBV) infection is closely related with the occurrence and development of hepatocellular carcinoma (HCC), in which Hepatitis B virus x protein (HBx) and core protein (HBc) play crucial roles. Additionally, inhibitors of differentiation (Id) proteins exhibited significant correlation with liver cancer development. Here, we identified that HBV dramatically inhibited the expression of Id1 and Id3 in both protein and transcriptional levels for the first time, whereas there was little effects of the virus on Id2. Additionally, two HBV coded protein, HBc and HBx, could reduce the expression of Id1 and Id3 distinctly, whereas the other two viral proteins, HBs and HBp were unable to affect theId1 and Id3 proteins. Both the activity inhibitors and activators further confirmed that HBc inhibited the expression of Id1 and Id3 by BMP/Smad signaling pathway. HBx could interact with both Id1 and Id3 at residues 112-136 of HBx protein, and it could inhibit the two Id proteins by accelerating their degradation. This is the first report about HBc and HBx regulating Id1 and Id3, whereas the detailed mechanism associated with above needed further experiments to clarify.

Copyright © 2020. Published by Elsevier B.V.
KEYWORDS:

HBV; HBc; HBx; Id1; Id3

PMID:
    32305567
DOI:
    10.1016/j.virusres.2020.197973

StephenW

病毒库。 2020年4月16日：197973。 doi：10.1016 / j.virusres.2020.197973。 [Epub提前发行]
乙型肝炎病毒的HBx和HBc可以通过降低其转录和稳定性来影响Id1和Id3。
夏L1，王S2，张H3，杨Y4，魏J4，施Y5，邹C5，刘J5，罗M6，黄A4，王D7。
作者信息

1个
    重庆医科大学传染病教研室，病毒性肝炎研究所，传染病分子生物学重点实验室（教育部）；重庆医科大学检验医学院，重庆。
2
    重庆市重庆市中医院皮肤美容科。
3
    重庆市妇女儿童保健中心临床实验室，重庆。
4
    重庆医科大学传染病教研室，病毒性肝炎研究所，传染病分子生物学教育部重点实验室（教育部）。
5
    重庆医科大学检验医学院，重庆。
6
    重庆市渝北区人民医院检验科。
7
    重庆医科大学传染病教研室，病毒性肝炎研究所，传染病分子生物学重点实验室（教育部）；重庆医科大学检验医学院，重庆。电子地址：[email protected]。

抽象

乙肝病毒（HBV）感染与肝细胞癌（HCC）的发生和发展密切相关，其中乙肝病毒x蛋白（HBx）和核心蛋白（HBc）起着至关重要的作用。此外，分化抑制剂（Id）蛋白质与肝癌的发展也显示出显着的相关性。在这里，我们发现HBV首次在蛋白质和转录水平上均显着抑制了Id1和Id3的表达，而该病毒对Id2的影响很小。此外，两种HBV编码蛋白HBc和HBx可以明显降低Id1和Id3的表达，而其他两种病毒蛋白HBs和HBp无法影响Id1和Id3的蛋白。活性抑制剂和活化剂都进一步证实了HBc通过BMP / Smad信号通路抑制了Id1和Id3的表达。 HBx可以在HBx蛋白的残基112-136与Id1和Id3相互作用，并且可以通过加速其降解来抑制这两种Id蛋白。这是有关HBc和HBx调节Id1和Id3的第一份报告，而与上述相关的详细机制还需要进一步的实验来阐明。

版权所有©2020。由Elsevier B.V.发布。
关键字：

乙肝病毒乙肝; HBx; Id1; ID3

PMID：
    32305567
DOI：
    10.1016 / j.virusres.2020.197973