二氟甲基鸟氨酸，一种脱羧酶1抑制剂，可通过降低HBc蛋白水

StephenW

Front Cell Infect Microbiol. 2020 Apr 16;10:158. doi: 10.3389/fcimb.2020.00158. eCollection 2020.
Difluoromethylornithine, a Decarboxylase 1 Inhibitor, Suppresses Hepatitis B Virus Replication by Reducing HBc Protein Levels.
Mao B1, Wang Z1, Pi S1, Long Q1, Chen K1, Cui J1, Huang A1, Hu Y1.
Author information

1
    Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.

Abstract

Current treatments of hepatitis B virus (HBV) are limited to Interferon-alpha or the nucleos(t)ide analogs antiviral therapies, and it is crucial to develop and define new antiviral drugs to cure HBV. In this study, we explored the anti-HBV effect of difluoromethylornithine (DFMO), an irreversibly inhibitor of decarboxylase 1(ODC1) on HBV replication. Firstly, we found that polyamines contributed to HBV DNA replication via increasing levels of the HBV core protein (HBc) and capsids. In contrast, depletion of polyamines either by silencing the expression of ODC1 or DFMO treatment, resulted in decreasing viral DNA replication and levels of HBc protein and capsids. Furthermore, we found that DFMO decreased the stability of the HBc protein without affecting mRNA transcription and protein translation. Taken together, our findings demonstrate that DFMO inhibits HBV replication by reducing HBc stability and this may provide a new approach for HBV therapeutics.

Copyright © 2020 Mao, Wang, Pi, Long, Chen, Cui, Huang and Hu.
KEYWORDS:

DFMO; HBc; ODC1; hepatitis B virus; polyamines

PMID:
    32373551
PMCID:
    PMC7176913
DOI:
    10.3389/fcimb.2020.00158

Free PMC Article

StephenW

前细胞感染微生物。 2020 Apr 16; 10：158。 doi：10.3389 / fcimb.2020.00158。 eCollection 2020。
二氟甲基鸟氨酸，一种脱羧酶1抑制剂，可通过降低HBc蛋白水平来抑制乙型肝炎病毒的复制。
毛B1，王Z1，皮S1，龙Q1，陈K1，崔J1，黄A1，胡Y1。
作者信息

1个
    重庆医科大学附属第二医院传染病科，传染病分子生物学教育部重点实验室，病毒性肝炎研究所

抽象

目前乙型肝炎病毒（HBV）的治疗仅限于干扰素-α或核苷酸（t）ide类似物抗病毒治疗，因此开发和定义新的抗病毒药物来治疗HBV至关重要。在这项研究中，我们探讨了二氟甲基鸟氨酸（DFMO）的抗HBV效应，DFMO是脱羧酶1（ODC1）的不可逆抑制剂，对HBV复制具有抗性。首先，我们发现多胺通过增加HBV核心蛋白（HBc）和衣壳的水平来促进HBV DNA复制。相比之下，通过沉默ODC1或DFMO处理的表达来消除多胺，会导致病毒DNA复制减少以及HBc蛋白和衣壳水平降低。此外，我们发现DFMO在不影响mRNA转录和蛋白翻译的情况下降低了HBc蛋白的稳定性。综上所述，我们的发现表明DFMO通过降低HBc稳定性来抑制HBV复制，这可能为HBV治疗提供一种新方法。

版权所有©2020毛，王，皮，龙，陈，崔，黄和胡。
关键字：

DFMO；乙肝; ODC1;乙型肝炎病毒;多胺

PMID：
    32373551
PMCID：
    PMC7176913
DOI：
    10.3389 / fcimb.2020.00158

免费PMC文章

StephenW

https://www.frontiersin.org/articles/10.3389/fcimb.2020.00158/pdf