The RNA Sensor RIG-I Dually Functions as an Innate Sensor and Direct Antiviral Factor for Hepatitis B Virus
The RNA Sensor RIG-I Dually Functions as an Innate Sensor and Direct Antiviral Factor for Hepatitis B Virus
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DOI：
10.1016/j.immuni.2014.12.016
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发表时间：
2015-01-20
期刊：
影响因子：
32.4
通讯作者：
Takaoka, Akinori
中科院分区：
文献类型：
--
作者：
Sato, Seiichi;Li, Kai;Takaoka, Akinori
宿主先天识别触发了病毒消除的关键免疫应答。B型肝炎病毒（HBV）是一种DNA病毒，其传感机制和随后的下游信号事件仍有待充分阐明。在此我们发现，通过视黄酸诱导基因I（RIG-I）介导的HBV前基因组RNA的5 '-端区域的感应，在人原代肝细胞中应答HBV感染主要诱导III型而非I型干扰素。此外，RIG-I还可以以RNA结合依赖的方式抵消HBV聚合酶（P蛋白）与5 '-HBc区域的相互作用，从而持续抑制病毒复制。脂质体介导的交付和载体为基础的表达，这e区来源的RNA在肝脏中废除了HBV复制在人肝细胞嵌合小鼠。这些发现确定了一种先天识别机制，通过该机制，RIG-I作为HBV传感器激活先天信号传导并抵消人肝细胞中的病毒聚合酶。
Host innate recognition triggers key immune responses for viral elimination. The sensing mechanism of hepatitis B virus (HBV), a DNA virus, and the subsequent downstream signaling events remain to be fully clarified. Here we found that type III but not type I interferons are predominantly induced in human primary hepatocytes in response to HBV infection, through retinoic acid-inducible gene-I (RIG-I)-mediated sensing of the 5'-epsilon region of HBV pregenomic RNA. In addition, RIG-I could also counteract the interaction of HBV polymerase (P protein) with the 5'-epsilon region in an RNA-binding dependent manner, which consistently suppressed viral replication. Liposome-mediated delivery and vector-based expression of this e region-derived RNA in liver abolished the HBV replication in human hepatocyte-chimeric mice. These findings identify an innate-recognition mechanism by which RIG-I dually functions as an HBV sensor activating innate signaling and to counteract viral polymerase in human hepatocytes.