Poly（C）-binding protein 1 （PCBP1） mediates housekeeping ：legradation of mitochondrial antiviral signaling （MAVS）

Mitochondrial antiviral signaling （MAVS） is a key adaptor in cellular antiviral innate immunity. We previously identified poly（C）-binding protein 2 （PCBP2） as a feedback inhibitor of MAVS that facilitates its degradation after viral infection, but little is known about the regulatory potential of poly（C）-binding protein 1 （PCBP1）, which highly resembles PCBP2. Here we report that PCBP1 mediates housekeeping degradation of MAVS using the same mecha- nism as PCBP2 employs. Overexpression of PCBP1 impairs MAVS-mediated antiviral responses, while knockdown of PCBP1 exerts the opposite effect. The suppression is due to PCBPl-induced MAVS degradation. We observe that PCBP1 and PCBP2 show synergy in MAVS inhibition, but their expression patterns are distinct： PCBP1 is stably and abundantly expressed, while PCBP2 shows low basal expression with rapid induction after infection. Individual knockdown and subcellular fractionation analyses reveal that unlike the postinfection inhibitor PCBP2, PCBP1 continuously eliminates cellular MAVS. Our findings unravel a critical role of PCBP1 in regulating MAVS for both finetuning the antiviral immunity and preventing inflammation.