Abstract
During virus infection, RIG-I-like receptors (RLRs) recognize viral RNAs and recruit the adaptor protein VISA to activate downstream signaling, leading to activation of transcription factors NF-κB and IRF3, which collaborate to induce type I interferons (IFNs). IFNs further induce expression of hundreds of IFN-stimulated genes (ISGs) that suppress viral replication and facilitate the adaptive immune response. Dysregulated production of IFNs is implicated in various immune diseases. Here we identified Signal Recognition Particle 54 (SRP54) as a negative regulator of RLRs-induced antiviral signaling. Overexpression of SRP54 inhibited RNA virus-triggered induction of IFN-β and increased viral replication, whereas knockdown of SRP54 had opposite effects. Mechanistically, SRP54 interacted with both RIG-I and MDA5 and impaired their association with VISA. Our findings demonstrate that SRP54 acts as a negative regulator of RLRs-mediated innate immune response by disrupting the recruitment of VISA to RIG-I/MDA5.
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Acknowledgements
This study was supported by the National Natural Science Foundation of China (31770946, awarded to Y.Y.) and Key Research Programs of Frontier Science (awarded to Y.Y.W.) funded by Chinese Academy of Sciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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DPW, YYW and YY designed the experiments. DPW, HYZ, BWL and TZ carried out the experiments. DPW, ZSX, YYW and YY analyzed the data. DPW wrote the paper. YY and YYW checked and finalized the manuscript. All authors read and approved the final manuscript.
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Wang, DP., Zhang, HY., Liao, BW. et al. SRP54 Negatively Regulates IFN-Beta Production and Antiviral Response by Targeting RIG-I and MDA5. Virol. Sin. 36, 231–240 (2021). https://doi.org/10.1007/s12250-020-00267-6
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DOI: https://doi.org/10.1007/s12250-020-00267-6