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新型泛素连接酶NIRF通过作用于乙肝病毒核心蛋白和组蛋白H3抑制乙肝病毒复制

NIRF, a Novel Ubiquitin Ligase, Inhibits Hepatitis B Virus Replication Through Effect on HBV Core Protein and H3 Histones.

作者信息

Qian Guanhua, Hu Bin, Zhou Danlin, Xuan Yanyan, Bai Lu, Duan Changzhu

机构信息

1 Department of Cell Biology and Medical Genetics, Chongqing Medical University , Chongqing, China .

出版信息

DNA Cell Biol. 2015 May;34(5):327-32. doi: 10.1089/dna.2014.2714. Epub 2015 Feb 9.

DOI:10.1089/dna.2014.2714
PMID:25664994
Abstract

Np95/ICBP90-like RING finger protein (NIRF), a novel E3 ubiquitin ligase, has been shown to interact with HBc and promote its degradation. This study investigated the effects of NIRF on replication of hepatitis B virus (HBV) and the mechanisms. We have shown that NIRF inhibits replication of HBV DNA and secretion of HBsAg and HBeAg in HepG2 cells transfected with pAAV-HBV1.3. NIRF also inhibits the replication and secretion of HBV in a mouse model that expressed HBV. NIRF reduces acetylation of HBV cccDNA-bound H3 histones. These results showed that NIRF is involved in the HBV replication cycle not only through direct interaction with HBc but also reduces acetylation of HBV cccDNA-bound H3 histones.

摘要

Np95/ICBP90样环指蛋白(NIRF)是一种新型E3泛素连接酶,已被证明可与乙肝核心蛋白(HBc)相互作用并促进其降解。本研究调查了NIRF对乙型肝炎病毒(HBV)复制的影响及其机制。我们发现,在转染了pAAV-HBV1.3的HepG2细胞中,NIRF可抑制HBV DNA的复制以及乙肝表面抗原(HBsAg)和乙肝e抗原(HBeAg)的分泌。NIRF在表达HBV的小鼠模型中也可抑制HBV的复制和分泌。NIRF可降低与HBV共价闭合环状DNA(cccDNA)结合的H3组蛋白的乙酰化水平。这些结果表明,NIRF不仅通过与HBc直接相互作用参与HBV复制周期,还可降低与HBV cccDNA结合的H3组蛋白的乙酰化水平。

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