Induction of Siglec-G by RNA Viruses Inhibits the Innate Immune Response by Promoting RIG-I Degradation
Induction of Siglec-G by RNA Viruses Inhibits the Innate Immune Response by Promoting RIG-I Degradation
复制标题
RNA 病毒诱导 Siglec-G 通过促进 RIG-I 降解来抑制先天免疫反应
DOI：
10.1016/j.cell.2013.01.011
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发表时间：
2013-01-31
期刊：
影响因子：
64.5
通讯作者：
Cao, Xuetao
中科院分区：
文献类型：
--
作者：
Chen, Weilin;Han, Chaofeng;Cao, Xuetao
RIG - I是一种关键的RNA病毒传感器，用于启动抗病毒先天免疫。然而，RIG - I信号通路的翻译后调控仍未被完全理解。我们在此报道，RNA病毒（而非DNA病毒或细菌）通过RIG - I或NF - κB依赖的机制特异性上调巨噬细胞中凝集素家族成员Siglecg的表达。Siglec - G诱导SHP2和E3泛素连接酶c - Cbl向RIG - I募集，导致c - Cbl在RIG - I的Lys813位点通过K48连接的泛素化使其降解。通过增加I型干扰素的产生，Siglecg的靶向失活可保护小鼠免受致命RNA病毒感染。综上所述，我们的数据揭示了RIG - I信号通路的一个负反馈回路，并确定了RNA病毒利用的由Siglec - G介导的免疫逃逸途径，这对抗病毒应用具有启示意义。这些发现也为已知的适应性反应调节因子Siglec - G在先天免疫中的功能和相互作用提供了见解。
RIG-I is a critical RNA virus sensor that serves to initiate antiviral innate immunity. However, post-translational regulation of RIG-I signaling remains to be fully understood. We report here that RNA viruses, but not DNA viruses or bacteria, specifically upregulate lectin family member Siglecg expression in macrophages by RIG-I-or NF-kappa B-dependent mechanisms. Siglec-G-induced recruitment of SHP2 and the E3 ubiquitin ligase c-Cbl to RIG-I leads to RIG-I degradation via K48-linked ubiquitination at Lys813 by c-Cbl. By increasing type I interferon production, targeted inactivation of Siglecg protects mice against lethal RNA virus infection. Taken together, our data reveal a negative feedback loop of RIG-I signaling and identify a Siglec-G-mediated immune evasion pathway exploited by RNA viruses with implication in antiviral applications. These findings also provide insights into the functions and crosstalk of Siglec-G, a known adaptive response regulator, in innate immunity.