The Ubiquitin Ligase Riplet Is Essential for RIG-I-Dependent Innate Immune Responses to RNA Virus Infection
The Ubiquitin Ligase Riplet Is Essential for RIG-I-Dependent Innate Immune Responses to RNA Virus Infection
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DOI：
10.1016/j.chom.2010.11.008
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发表时间：
2010-12-16
影响因子：
30.3
通讯作者：
Seya, Tsukasa
中科院分区：
文献类型：
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作者：
Oshiumi, Hiroyuki;Miyashita, Moeko;Seya, Tsukasa
RNA病毒感染由RIG-I样受体RIG-I和MDA 5识别，其诱导抗病毒应答，包括I型干扰素（IFN）和促炎细胞因子的产生。RIG-I受Lys 63连接的多聚泛素化的调节，据报道，三种E3泛素连接酶RNF 125、TRIM 25和Rip let靶向RIG-I进行泛素化。为了检查Rip let在体内的重要性，我们产生了Rip let缺陷小鼠。成纤维细胞，巨噬细胞，和传统的树突状细胞从Riplet缺陷的动物是有缺陷的IFN和其他细胞因子的生产响应感染的几种RNA病毒。然而，Rip let在响应B-DNA和DNA病毒感染时产生IFN是不确定的。在RNA病毒感染过程中，Rip let缺陷消除了RIG-I的激活，并且突变小鼠比野生型小鼠更容易感染水疱性口炎病毒。这些数据表明，Rip let对于体内调节RIG-I介导的针对RNA病毒感染的先天免疫应答是必需的。
RNA virus infection is recognized by the RIG-I-like receptors RIG-I and MDA5, which induce antiviral responses including the production of type I interferons (IFNs) and proinflammatory cytokines. RIG-I is regulated by Lys63-linked polyubiquitination, and three E3 ubiquitin ligases, RNF125, TRIM25, and Rip let, are reported to target RIG-I for ubiquitination. To examine the importance of Rip let in vivo, we generated Rip let-deficient mice. Fibroblasts, macrophages, and conventional dendritic cells from Riplet-deficient animals were defective for the production of IFN and other cytokines in response to infection with several RNA viruses. However, Rip let was dispensable for the production of IFN in response to B-DNA and DNA virus infection. Rip let deficiency abolished RIG-I activation during RNA virus infection, and the mutant mice were more susceptible to vesicular stomatitis virus infection than wild-type mice. These data indicate that Rip let is essential for regulating RIG-I-mediated innate immune response against RNA virus infection in vivo.