TRIM14 is a mitochondrial adaptor that facilitates retinoic acid-inducible gene-I-like receptor-mediatedinnate immune response

Abstract

Innate immunity provides the first line of host defense againstinvading microbial pathogens. This defense involves retinoic acid-inducible gene-I-like receptors that detect viral RNA and activatethe mitochondrial antiviral-signaling (MAVS) protein, an adaptorprotein, leading to activation of the innate antiviral immune response. The mechanisms by which the MAVS signalosome assembles on mitochondria are only partially understood. Here, weidentify tripartite motif 14 (TRIM14) as a mediator in the immuneresponse against viral infection. TRIM14 localizes to the outermembrane of mitochondria and interacts with MAVS. Upon viralinfection, TRIM14 undergoes Lys-63-linked polyubiquitination atLys-365 and recruits NF-KB essential modulator to the MAVS sig-nalosome, leading to the activation of both the IFN regulatoryfactor 3 and NF-KB pathways. Knockdown of TRIM14 disruptsthe association between NF-KB essential modulator and MAVSand attenuates the antiviral response. Our results indicate thatTRIM14 is a component of the mitochondrial antiviral immunitythat facilitates the immune response mediated by retinoic acid-inducible gene-I-like receptors.