Hepatitis B virus inhibits intrinsic RIG-I and RIG-G immune signaling via inducing miR146a.
Hepatitis B virus inhibits intrinsic RIG-I and RIG-G immune signaling via inducing miR146a.
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DOI：
10.1038/srep26150
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发表时间：
2016-05-23
影响因子：
4.6
通讯作者：
Tian Z
中科院分区：
文献类型：
--
作者：
Hou Z;Zhang J;Han Q;Su C;Qu J;Xu D;Zhang C;Tian Z
以往的研究表明，乙型肝炎病毒（Hepatitis B Virus，HBV）作为潜伏入侵者，会减弱宿主的抗病毒免疫反应。miRNAs参与HBV感染和HBV相关疾病的发生，但miRNAs在HBV介导的免疫抑制中的确切作用尚不清楚。在此，我们观察到，下调RIG-I样受体可能是HBV诱导的HBV+肝癌细胞系和肝癌组织中I型IFN转录抑制的一个关键机制。然后，证明miR 146 a通过直接靶向RIG-I和RIG-G两者来负调节RIG-I样受体的表达。进一步的研究表明，通过反义抑制剂或海绵方法拮抗miR 146 a在体外和携带HBV的小鼠模型中加速HBV清除并降低HBV载量。因此，我们的研究结果表明，HBV诱导的miR 146 a通过靶向RIG-I和RIG-G减弱细胞固有的抗病毒先天免疫，沉默miR 146 a可能是逆转HBV诱导的免疫抑制的有效靶点。
Previous studies showed that hepatitis B virus (HBV), as a latency invader, attenuated host anti-viral immune responses. miRNAs were shown to be involved in HBV infection and HBV-related diseases, however, the precise role of miRNAs in HBV-mediated immunosuppression remains unclear. Here, we observed that down-regulated RIG-I like receptors might be one critical mechanism of HBV-induced suppression of type I IFN transcription in both HBV+ hepatoma cell lines and liver cancer tissues. Then, miR146a was demonstrated to negatively regulate the expression of RIG-I-like receptors by directly targeting both RIG-I and RIG-G. Further investigation showed that antagonizing miR146a by anti-sense inhibitors or sponge approach accelerated HBV clearance and reduced HBV load both in vitro and in a HBV-carrying mouse model. Therefore, our findings indicated that HBV-induced miR146a attenuates cell-intrinsic anti-viral innate immunity through targeting RIG-I and RIG-G, and silencing miR146a might be an effective target to reverse HBV-induced immune suppression.