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SOX9 negatively regulates the RLR antiviral signaling by targeting MAVS

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Abstract

Mitochondrial virus-induced signal adaptor (MAVS), also known as VISA, IPS-1, and Cardif, is a crucial adaptor protein in the RIG-I-like receptor (RLR) signaling pathway. Upon viral infection, RIG-I recognizes viral dsRNA and further transfers it to mitochondria, where it binds to MAVS through its CARD domain, generating a series of signal cascades. Transduction through this signaling cascade leads to phosphorylation and nuclear translocation of interferon regulatory factor 3/7 (IRF3/IRF7) and activation of NF-κB, which ultimately produces type I interferon (IFN) and proinflammatory cytokines. Here, our experiments demonstrated that overexpression of SRY-related high-mobility group protein 9 (SOX9) significantly inhibited Sendai virus (SeV)-induced and MAVS-mediated activation of the IFN-β promoter and ISRE. However, knocking out the expression of SOX9 in cells promoted SeV-induced IFN-β promoter and ISRE activation. Further studies have shown that SOX9 interacts with MAVS and targets MAVS to inhibit the association of MAVS-TRAF2, thereby inhibiting MAVS-mediated TRAF2 ubiquitination. Taken together, these results indicate that SOX9 downregulates IFN-β expression and antiviral signal transduction by targeting MAVS.

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Acknowledgements

We are grateful to Dr. Hong-Bing Shu (Medical Research Institute, Wuhan University) for providing plasmids and other reagents. This work was supported by grants from the National Natural Science Foundation of China (Grant Nos. 81971502, 82060298).

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  1. College of Life Science, Jiangxi Normal University, 99 Ziyang Road, Nanchang, 330022, Jiangxi, China

    Xue Jiang & Liang-Guo Xu

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  1. Xue Jiang
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LX designed the research. XJ performed the experiments. LX and XJ did data analysis and discussion. XJ and LX wrote the manuscript.

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Correspondence to Liang-Guo Xu.

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Jiang, X., Xu, LG. SOX9 negatively regulates the RLR antiviral signaling by targeting MAVS. Virus Genes 58, 122–132 (2022). https://doi.org/10.1007/s11262-022-01886-9

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