期刊
CELL
卷 152, 期 3, 页码 467-478出版社
CELL PRESS
DOI: 10.1016/j.cell.2013.01.011
关键词
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资金
- National Key Basic Research Program of China [2013CB530500, 2012CB910202]
- National Natural Science Foundation of China [81273222, 81230074, 81123006]
- National 125 Key Project [2012ZX10002-014, 2012AA020901]
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.
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