TRIM26 Negatively Regulates Interferon-β Production and Antiviral Response through Polyubiquitination and Degradation of Nuclear IRF3

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Innate immunity is the first line of defense to protect host from infection of invading pathogens. Production of type I inteferons by the innate immune cells is pivotal for the cellular antiviral immune responses. After virus infection, IFN-β transcription requires IRF3, which is activated through phosphorylation, dimerization and nuclear translocation. Although IRF3 activation and IFN-β production are essential for the host to prevent viral infection, aberrant or excessive IFN-β production may lead to the pathogenesis of human autoimmune diseases. Therefore, IRF3 activation and IFN-β production must be terminated at the appropriate time points after viral infection. Degradation of IRF3 in the nucleus represents a novel mechanism to terminate IFN-β production. Here we identified TRIM26 as a novel E3 ligase to target nuclear IRF3. TRIM26 attenuated IFN-β production through polyubiquitination and degradation of nuclear IRF3. In vivo experiments with TRIM26 transgenic mice further confirmed the negative function of TRIM26 on IFN-β production and antiviral responses. Given that IRF3 is a common molecule downstream of TLR3, RLRs and intracellular DNA signaling pathways, our study identified a novel mechanism to limit RNA and DNA virus-induced signaling, inflammation and tissue injury and provided new clues for the treatment of autoimmune diseases.

Vyšlo v časopise: TRIM26 Negatively Regulates Interferon-β Production and Antiviral Response through Polyubiquitination and Degradation of Nuclear IRF3. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004726
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004726

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