题名: |
Induction of Siglec-G by RNA Viruses Inhibits the Innate Immune Response by Promoting RIG-I Degradation |
作者: |
Weilin Chen, Chaofeng Han, Bin Xie, Xiang Hu, Qian Yu, Liyun Shi, Qingqing Wang, Dongling Li, Jianli Wang, Pan Zheng, Yang Liu, Xuetao Cao |
单位: |
Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China |
出处: |
Cell,2013,152(Issue 3):467-478 |
语种: |
英文 |
文摘: |
RIG-I is a critical RNA virus sensor that serves to initiate antiviral innate immunity. However, posttranslational 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 Siglecgexpression in macrophages by RIG-I- or NF-κB-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. |
关键词: |
Siglec-G; RNA Viruses; Innate Immune Response;RIG-I Degradation |
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