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
Weilin Chen, et al. 2013. Cell 152, 467–478
Speaker: Kai-Fei Chang (張凱斐) Time: 14:00~15:00, Apr. 17, 2013
Commentator: Dr. Pin Ling (凌斌 老師) Place: Room 601
Abstract:
Sialic acid-binding immunoglobulin-like lectin (Siglec) family proteins belong to the immunoglobulin superfamily and recognize sialic acid-containing glycans on the surface of pathogens. Siglec-G is a Siglec family member. Previous study showed that Siglec-G contains an intracellular domain possessing immunoreceptor tyrosine-based inhibition motif and restricts B cell receptor signaling1. RIG-I is a family member of RIG-I-like receptors and detects viral RNA in cytoplasm. When RIG-I recognizes viral RNA, its downstream signaling triggers antiviral gene expression and leads to the production of inflammatory cytokines2. In this article, the authors found that Siglec-G expression was upregulated during virus infection. They also found that type I interferon production was increased in Siglec-G-deficient mice. Siglec-G-deficient macrophages produced high levels of RIG-I during RNA virus infection. These findings suggest that Siglec-G negatively regulates RIG-I protein expression. The authors demonstrated that Siglec-G interacted with the E3 ligase c-Cbl to promote protein ubiquitination and degradation of RIG-I via proteasomal pathway. Moreover, active Siglec-G recruited tyrosine phosphatase SHP2 for promoting the interaction of RIG-I with Siglec-G and RIG-I degradation during virus infection. Lysine 813 of RIG-I protein was essential for its ubiquitination and degradation. In conclusion, Siglec-G promotes c-Cbl- and SHP2-mediated degradation of RIG-I for downregulating innate immunity during RNA virus infection.
References:
1. Hoffmann, A., Kerr, S., Jellusova, J., Zhang, J., Weisel, F., Wellmann, U., Winkler, T.H., Kneitz, B., Crocker, P.R., and Nitschke, L. (2007). Siglec-G is a B1 cell-inhibitory receptor that controls expansion and calcium signaling of the B1 cell population. Nat. Immunol. 8, 695–704.
2. Loo, Y.M., and Gale, M. Jr. (2011). Immune signaling by RIG-I-like receptors. Immunity 34, 680-692.