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Virus-inducible IGFALS facilitates innate immune responses by mediating IRAK1 and TRAF6 activation

Cellular & Molecular Immunology volume 18, pages 1587–1589 (2021)Cite this article

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Activation of TLR signaling is a first line of the host defense system in the elimination of invading pathogens.1 Insulin-like growth factor binding protein, acid-labile subunit (IGFALS) is a leucine-rich glycoprotein. By prolonging the half-life of IGF-I in the vascular system,2 IGFALS regulates the bioavailability of IGF, which is crucial for normal growth and development and metabolic regulation.3,4 However, the role of IGFALS in antiviral innate immune responses has not been established. In this study, we found that IGFALS is virus inducible, while it in turn inhibits viral replication. Mechanistically, IGFALS directly associates with IRAK1 and TRAF6, facilitating IRAK1/TRAF6 complex formation and enhancing K63-linked polyubiquitination of both proteins for full activation, thereby facilitating antiviral signaling.

Activation of antiviral signaling cascades leads to the production of type I and III interferons (IFNs).5 The results of qPCR experiments indicated that overexpression of IGFALS potentiated VSV-induced IFN production (Fig. 1F). Furthermore, we generated IGFALS-deficient splenocytes; the qPCR analysis results demonstrated that IGFALS deletion inhibited the transcription of IFNs in these cells (Fig. 1G). In addition, we intranasally administered a lethal dose of IAV to IGFALS KO mice and WT mice and found that IFN production in the lungs was inhibited by IGFALS deficiency (Fig. 1H).

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Acknowledgements

This work was supported by a research grant from the National Natural Science Foundation of China (81971494).

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Authors and Affiliations

  1. State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China

    Gang Xu, Feiyan Deng, Qi Zuo, Lin Liu, Kaiwen Dou, Zhikui Cheng, Wei Cao, Chuanjin Luo, Chen Yu, Shi Liu & Ying Zhu

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  1. Gang Xu
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  2. Feiyan Deng
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  3. Qi Zuo
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  4. Lin Liu
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  6. Zhikui Cheng
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  7. Wei Cao
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  8. Chuanjin Luo
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  9. Chen Yu
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  10. Shi Liu
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  11. Ying Zhu
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Contributions

G.X. and Y.Z. conceived and designed the research. G.X. performed the research and analyzed the data. F.D., Q.Z., L.L., K.D., Z.C., W.C., C.L., C.Y., and S.L. contributed to performing the experiments and participated in discussion. Y.Z. contributed critical reagents. G.X. and Y.Z. wrote the manuscript with editorial input from all authors.

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Correspondence to Ying Zhu.

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The authors declare no competing interests.

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Xu, G., Deng, F., Zuo, Q. et al. Virus-inducible IGFALS facilitates innate immune responses by mediating IRAK1 and TRAF6 activation. Cell Mol Immunol 18, 1587–1589 (2021). https://doi.org/10.1038/s41423-021-00649-0

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