Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku Sapporo 060-8638, Japan.
Cell Host Microbe. 2010 Dec 16;8(6):496-509. doi: 10.1016/j.chom.2010.11.008.
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 Riplet, are reported to target RIG-I for ubiquitination. To examine the importance of Riplet in vivo, we generated Riplet-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, Riplet was dispensable for the production of IFN in response to B-DNA and DNA virus infection. Riplet 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 Riplet is essential for regulating RIG-I-mediated innate immune response against RNA virus infection in vivo.
RNA 病毒感染被 RIG-I 样受体 RIG-I 和 MDA5 识别，这些受体诱导抗病毒反应，包括产生 I 型干扰素（IFN）和促炎细胞因子。RIG-I 通过 Lys63 连接的多泛素化调节，有三种 E3 泛素连接酶，RNF125、TRIM25 和 Riplet，被报道将 RIG-I 作为泛素化的靶标。为了研究 Riplet 在体内的重要性，我们生成了 Riplet 缺陷型小鼠。来自 Riplet 缺陷型动物的成纤维细胞、巨噬细胞和常规树突状细胞在感染几种 RNA 病毒时，IFN 和其他细胞因子的产生存在缺陷。然而，Riplet 对于 B-DNA 和 DNA 病毒感染诱导 IFN 的产生是可有可无的。Riplet 缺陷消除了 RNA 病毒感染期间 RIG-I 的激活，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，Riplet 对于调节 RIG-I 介导的针对 RNA 病毒感染的先天免疫反应在体内是必不可少的。
