宿主因子PRPF31参与HBV复制细胞中的cccDNA生产

StephenW

Biochem Biophys Res Commun. 2016 Nov 15. pii: S0006-291X(16)31948-9. doi: 10.1016/j.bbrc.2016.11.085. [Epub ahead of print]
Host factor PRPF31 is involved in cccDNA production in HBV-replicating cells.Kinoshita W1, Ogura N2, Watashi K3, Wakita T4.
Author information

• 1Central Pharmaceutical Research Institute, Japan Tobacco Inc., Osaka, Japan. Electronic address: [email protected].
• 2Central Pharmaceutical Research Institute, Japan Tobacco Inc., Osaka, Japan. Electronic address: [email protected].
• 3Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan. Electronic address: [email protected].
• 4Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan. Electronic address: [email protected].
  

AbstractHepatitis B virus (HBV) covalently closed circular DNA (cccDNA) plays a central role in chronic HBV infection and replication, and is an important factor for HBV surface antigen loss indicating the endpoint of HBV treatment. However, there is a known problem that current anti-HBV drugs, including interferons and nucleos(t)ide analogues, reduce HBV replication but have a little or no effect on reducing cccDNA. Therefore, the development of new therapeutic agents is necessary to eradicate cccDNA. In this study, we identified pre-mRNA processing factor 31 (PRPF31) by siRNA screening as a factor associated with cccDNA. PRPF31 knockdown by siRNA decreased cccDNA formation without serious cytotoxicity. In rescue experiments, expression of siRNA-resistant PRPF31 recovered cccDNA formation. PRPF31 knockdown did not affect HBV core protein and HBV core DNA levels in HBV-replicating cells. Chromatin immunoprecipitation and immunoprecipitation assays revealed an association between PRPF31 and cccDNA. Furthermore, co-overexpression of PRPF31 and HBx enhanced cccDNA formation in HepAD38 cells. Taken together, the present findings suggest that the interaction between PRPF31 and HBx may be a novel target for anti-HBV treatment.

Copyright © 2016. Published by Elsevier Inc.

KEYWORDS: HBV; PRPF31; cccDNA

PMID:27864147DOI:10.1016/j.bbrc.2016.11.085

StephenW

Biochem Biophys Res Commun。 2016 Nov 15. pii：S0006-291X（16）31948-9。 doi：10.1016 / j.bbrc.2016.11.085。 [打印前的电子版]
宿主因子PRPF31参与HBV复制细胞中的cccDNA生产。
Kinoshita W1，Ogura N2，Watashi K3，Wakita T4。
作者信息

    1中央药物研究所，日本烟草公司，日本大阪。电子地址：[email protected]。
    2Central Pharmaceutical Research Institute，Japan Tobacco Inc.，Osaka，Japan。电子地址：[email protected]。
    3病毒学II，国立传染病研究所，日本东京。电子地址：[email protected]。
    4病毒学II，国家传染病研究所，日本东京。电子地址：[email protected]。

抽象

乙型肝炎病毒（HBV）共价闭合环状DNA（cccDNA）在慢性HBV感染和复制中起中心作用，并且是指示HBV治疗终点的HBV表面抗原损失的重要因素。然而，存在已知的问题，即目前的抗HBV药物，包括干扰素和核苷酸类似物，减少HBV复制，但对减少cccDNA具有很小或没有影响。因此，开发新的治疗剂是消除cccDNA所必需的。在这项研究中，我们确定前mRNA加工因子31（PRPF31）通过siRNA筛选作为与cccDNA相关的因素。 PRPF31敲低siRNA减少cccDNA形成没有严重的细胞毒性。在拯救实验中，siRNA抗性PRPF31的表达回收cccDNA形成。 PRPF31敲低不影响HBV核心蛋白和HBV核心DNA水平在HBV复制的细胞。染色质免疫沉淀和免疫沉淀测定显示PRPF31和cccDNA之间的关联。此外，共同过表达的PRPF31和HBx增强肝癌细胞中的cccDNA形成。总之，本发现表明PRPF31和HBx之间的相互作用可能是抗HBV治疗的新目标。

版权所有©2016 Elsevier Inc.
关键词：

HBV; PRPF31; cccDNA

PMID：
    27864147
DOI：
    10.1016 / j.bbrc.2016.11.085

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