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: Weilin Chen, Chaofeng Han, Bin Xie, Xiang Hu, Qian Yu, Liyun Shi, Qingqing Wang, Dongling Li, Jianli Wang, Pan Zheng, Yang Liu, Xuetao Cao
• Journal: Cell (Cell) Vol. 152 Issue 3 Pg. 467-78 (Jan 31 2013) ISSN: 1097-4172 [Electronic] United States
• PMID: 23374343 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Interferon Regulatory Factor-3
• Irf3 protein, mouse
• Lectins
• NF-kappa B
• Receptors, Antigen, B-Cell
• Sialic Acid Binding Immunoglobulin-like Lectins
• Siglecg protein, mouse
• Proto-Oncogene Proteins c-cbl
• Protein Tyrosine Phosphatase, Non-Receptor Type 11
• Ptpn11 protein, mouse
• Ddx58 protein, mouse
• DEAD Box Protein 58
• DEAD-box RNA Helicases
• Cbl protein, mouse
• Lysine

Topics

• Animals
• DEAD Box Protein 58
• DEAD-box RNA Helicases (chemistry, metabolism)
• Dendritic Cells (immunology)
• Gram-Negative Bacteria (metabolism)
• Gram-Negative Bacterial Infections (immunology)
• Immunity, Innate
• Interferon Regulatory Factor-3 (metabolism)
• Lectins (genetics, metabolism)
• Lysine (metabolism)
• Macrophages (immunology)
• Mice
• Mice, Inbred C57BL
• NF-kappa B (metabolism)
• Protein Tyrosine Phosphatase, Non-Receptor Type 11 (metabolism)
• Proto-Oncogene Proteins c-cbl (metabolism)
• RNA Virus Infections (immunology)
• RNA Viruses (metabolism)
• Receptors, Antigen, B-Cell (genetics, metabolism)
• Sialic Acid Binding Immunoglobulin-like Lectins
• Ubiquitination