DYRK4 upregulates antiviral innate immunity by promoting IRF3 activation.

ABSTRACT: Viral infection activates the transcription factors IRF3 and NF-κB, which induce type I interferon (IFN) and antiviral innate immune responses. Here, we identify dual-specific tyrosine phosphorylation-regulated kinase 4 (DYRK4) as an important regulator of virus-triggered IFN-β induction and antiviral innate immunity. Overexpression of DYRK4 enhances virus-triggered activation of IRF3 and type I IFN induction, whereas knockdown or knockout of DYRK4 impairs virus-induced activation of IRF3 and NF-κB. Moreover, Dyrk4-knockout mice are more susceptible to viral infection. The underlying mechanism involves DYRK4 acting as a scaffold protein to recruit TRIM71 and LUBAC to IRF3, increasing IRF3 linear ubiquitination, maintaining IRF3 stability and activation during viral infection, and promoting

SUBMITTER: Zeng X 

PROVIDER: S-EPMC11811199 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature