Identification of TRIM14 as a Type I IFN-Stimulated Gene Controlling Hepatitis B Virus Replication by Targeting HBx.
Identification of TRIM14 as a Type I IFN-Stimulated Gene Controlling Hepatitis B Virus Replication by Targeting HBx.
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鉴定 TRIM14 作为 I 型 IFN 刺激基因，通过靶向 HBx 控制乙型肝炎病毒复制
DOI：
10.3389/fimmu.2018.01872
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发表时间：
2018
影响因子：
7.3
通讯作者：
Cheng G
中科院分区：
文献类型：
--
作者：
Tan G;Xu F;Song H;Yuan Y;Xiao Q;Ma F;Qin FX;Cheng G
B型肝炎病毒（HBV）是世界范围内威胁人类健康的主要肝病病因。I型干扰素（IFN-1）治疗是HBV患者的重要治疗选择。IFN的抗病毒作用主要通过上调下游IFN刺激基因的表达来介导。然而，IFN诱导ISG产生和抑制HBV复制的机制尚未阐明。TRIM 14最近被报道为IFN信号通路中的关键分子，其调节响应于病毒感染的IFN产生。在这项研究中，我们试图了解IFN限制HBV复制的机制。我们证实了TRIM 14是肝细胞中的ISG，并且模式识别受体配体polyI：C和polydAdT诱导TRIM 14依赖于IFN-I的产生。此外，IFN-1激活的STAT 1（而不是STAT 3）直接结合到TRIM 14启动子并介导TRIM 14的诱导。有趣的是，TRIM 14在IFN-1介导的HBV复制抑制中起重要作用，TRIM 14 SPRY结构域与HBx的C端相互作用，可能通过抑制Smc-HBx-DDB 1复合物的形成而阻断HBx促进HBV复制的作用。因此，我们的研究清楚地表明，TRIM 14是STAT 1依赖性ISG，IFN-I-TRIM 14-HBx轴显示了理解IFN-I抑制病毒复制机制的另一种方式。
Hepatitis B virus (HBV) remains a major cause of hepatic disease that threatens human health worldwide. Type I IFN (IFN-I) therapy is an important therapeutic option for HBV patients. The antiviral effect of IFN is mainly mediated via upregulation of the expressions of the downstream IFN-stimulated genes. However, the mechanisms by which IFN induces ISG production and inhibits HBV replication are yet to be clarified. TRIM14 was recently reported as a key molecule in the IFN-signaling pathway that regulates IFN production in response to viral infection. In this study, we sought to understand the mechanisms by which IFN restricts HBV replication. We confirmed that TRIM14 is an ISG in the hepatic cells, and that the pattern-recognition receptor ligands polyI:C and polydAdT induce TRIM14 dependent on IFN-I production. In addition, IFN-I-activated STAT1 (but not STAT3) directly bound to the TRIM14 promoter and mediated the induction of TRIM14. Interestingly, TRIM14 played an important role in IFN-I-mediated inhibition of HBV, and the TRIM14 SPRY domain interacted with the C-terminal of HBx, which might block the role of HBx in facilitating HBV replication by inhibiting the formation of the Smc-HBx–DDB1 complex. Thus, our study clearly demonstrates that TRIM14 is a STAT1-dependent ISG, and that the IFN-I–TRIM14–HBx axis shows an alternative way to understand the mechanism by which IFN-I inhibits virus replication.
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影响因子：
25.7
作者：
Niu, Congrong;Li, Li;Fletcher, Simon P.
通讯作者：
Fletcher, Simon P.
DOI：
10.1038/nri2413
发表时间：
2008-11
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Ozato K;Shin DM;Chang TH;Morse HC 3rd
通讯作者：
Morse HC 3rd
影响因子：
5.4
作者：
Bergametti, F;Sitterlin, D;Transy, C
通讯作者：
Transy, C
影响因子：
25.7
作者：
Liu, Shi;Peng, Nanfang;Zhu, Ying
通讯作者：
Zhu, Ying
影响因子：
5.4
作者：
Keasler, Victor V.;Hodgson, Amanda J.;Slagle, Betty L.
通讯作者：
Slagle, Betty L.