title: Induction of Siglec-G by RNA viruses inhibits the innate immune response by promoting RIG-I degradation.
abstract: 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 Siglecg expression 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.
authors: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors: Weilin
authors: W
authors: Chen
authors: Chaofeng
authors: C
authors: Han
authors: Bin
authors: B
authors: Xie
authors: Xiang
authors: X
authors: Hu
authors: Qian
authors: Q
authors: Yu
authors: Liyun
authors: L
authors: Shi
authors: Qingqing
authors: Q
authors: Wang
authors: Dongling
authors: D
authors: Li
authors: Jianli
authors: J
authors: Wang
authors: Pan
authors: P
authors: Zheng
authors: Yang
authors: Y
authors: Liu
authors: Xuetao
authors: X
authors: Cao
mesh_terms: D000818:Animals; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000737:chemistry / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology; D006090:Gram-Negative Bacteria / Q000378:metabolism; D016905:Gram-Negative Bacterial Infections / Q000276:immunology*; D007113:Immunity, Innate; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D037102:Lectins / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism; D050721:Proto-Oncogene Proteins c-cbl / Q000378:metabolism; D012327:RNA Virus Infections / Q000276:immunology*; D012328:RNA Viruses / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism*; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D054875:Ubiquitination
chemical_list: D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; D037102:Lectins; D016328:NF-kappa B; D011947:Receptors, Antigen, B-Cell; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C522403:Siglecg protein, mouse; D050721:Proto-Oncogene Proteins c-cbl; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; C516725:Ptpn11 protein, mouse; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; C493849:Cbl protein, mouse; D008239:Lysine