Zebrafish RBM47 Promotes Lysosome-Dependent Degradation of MAVS to Inhibit IFN Induction

Abstract

IFN is essential for hosts to defend against viral invasion, whereas it must be tightly regulated to prevent hyperimmune responses. Fish mitochondrial antiviral signaling protein (MAVS) is a vital factor for IFN production, but until now, there have been few studies on the regulation mechanisms of fish MAVS enabling IFN to be properly controlled. In this study, we show that zebrafish RNA-binding motif protein 47 (RBM47) promotes MAVS degradation in a lysosome-dependent manner to suppress IFN production. First, the transcription of IFN activated by polyinosinic/polycytidylic acid (poly I:C), spring viremia of carp virus, or retinoic acid–inducible gene I (RIG-I)–like receptor pathway components were significantly suppressed by RBM47. Second, RBM47 interacted with MAVS and promoted lysosome-dependent degradation of MAVS, changing the cellular location of MAVS from the cytoplasm to the lysosome region. Finally, RBM47 inhibited downstream MITA and IRF3/7 activation, impairing the host antiviral response. Collectively, these data suggest that zebrafish RBM47 negatively regulates IFN production by promoting lysosome-dependent degradation of MAVS, providing insights into the role of RBM47 in the innate antiviral immune response in fish.