Ste20-Like Kinase TAOK1 Positively Regulates Rig-I Triggered Antiviral Innate Immune Response

Viral infection is one of the most dangerous factors that threaten human health and survival.Its constantly changing characteristics and the emergence of new unknown viruses are huge challenges facing modern medicine and life sciences.When a virus infects the body,pattern recognition receptors in the body recognize pathogen-associated pattern molecules in pathogenic microorganisms as a necessary prerequisite for triggering the natural immune response.As a key cytosolic sensor for detection of RNA viruses,retinoic-acid-inducible gene I(RIG-I)signal transduction has been regulated by several positive and negative mechanisms including phosphorylation.Here we show that viral infection down-regulates Thousand and one kinase1(TAOK1)expression in macrophages.TAOK1 promotes the RNA viruses-induction of type I interferon and interleukine-6(IL-6).TAOK1 deficient mice are more susceptible to viral infection.Mechanistically,TAOK1 enhances IRF3 and NF-?B activatin by binding to RIG-I in a kinase domain dependent manner and decreasing RIG-I phosphorylation,thereby enhancing RIG-I/MAVS complex formation.Our results identify TAOK1 as a new interacting parter for RIG-I.These findings provide novel insights into the function of TAOK1 in antiviral innate immune response and its related clinical significance.