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MCPIP1 reduces HBV-RNA by targeting its epsilon structure
Scientific Reports ( IF 4.6 ) Pub Date : 2020-11-27 , DOI: 10.1038/s41598-020-77166-z
Yingfang Li , Lusheng Que , Kento Fukano , Miki Koura , Kouichi Kitamura , Xin Zheng , Takanobu Kato , Hussein Hassan Aly , Koichi Watashi , Senko Tsukuda , Hideki Aizaki , Noriyuki Watanabe , Yuko Sato , Tadaki Suzuki , Hiroshi I. Suzuki , Kazuyoshi Hosomichi , Makoto Kurachi , Kousho Wakae , Masamichi Muramatsu

Hepatitis B virus (HBV) is the major causative factor of chronic viral hepatitis, liver cirrhosis, and hepatocellular carcinoma. We previously demonstrated that a proinflammatory cytokine IL-1β reduced the level of HBV RNA. However, the mechanism underlying IL-1β-mediated viral RNA reduction remains incompletely understood. In this study, we report that immune regulator Monocyte chemotactic protein-1-induced protein 1 (MCPIP1) can reduce HBV RNA in hepatocytes. MCPIP1 expression level was higher in the liver tissue of HBV-infected patients and mice. Overexpression of MCPIP1 decreased HBV RNA, whereas ablating MCPIP1 in vitro enhanced HBV production. The domains responsible for RNase activity or oligomerization, were required for MCPIP1-mediated viral RNA reduction. The epsilon structure of HBV RNA was important for its antiviral activity and cleaved by MCPIP1 in the cell-free system. Lastly, knocking out MCPIP1 attenuated the anti-HBV effect of IL-1β, suggesting that MCPIP1 is required for IL-1β-mediated HBV RNA reduction. Overall, these results suggest that MCPIP1 may be involved in the antiviral effect downstream of IL-1β.



中文翻译:

MCPIP1通过靶向其ε结构来降低HBV-RNA

乙型肝炎病毒(HBV)是慢性病毒性肝炎,肝硬化和肝细胞癌的主要病因。先前我们证明了促炎细胞因子IL-1β降低了HBV RNA的水平。但是,IL-1β介导的病毒RNA还原的机制尚不完全清楚。在这项研究中,我们报告免疫调节单核细胞趋化蛋白1诱导蛋白1(MCPIP1)可以减少肝细胞中的HBV RNA。HBV感染患者和小鼠肝脏组织中MCPIP1表达水平较高。MCPIP1的过表达降低了HBV RNA,而体外消融MCPIP1则提高了HBV的产生。MCPIP1介导的病毒RNA还原需要负责RNase活性或寡聚的域。HBV RNA的ε结构对其抗病毒活性很重要,并在无细胞系统中被MCPIP1裂解。最后,敲除MCPIP1减弱了IL-1β的抗HBV效应,表明MCPIP1是IL-1β介导的HBV RNA还原所必需的。总体而言,这些结果表明MCPIP1可能参与IL-1β下游的抗病毒作用。

更新日期:2020-11-27
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