gga-miR-142-5p attenuates IRF7 signaling and promotes replication of IBDV by directly targeting the chMDA5's 3' untranslated region.

Chicken melanoma differentiation-associated gene 5 (chMDA5) is a key pattern recognition receptor (PRR) that recognizes RNA viral infections and initiates an antiviral innate immune response in chickens. MicroRNAs (miRNAs) are involved in the regulation of chMDA5 to sense RNA virus infection, but how it exerts antiviral activity against infectious bursal disease virus (IBDV) infection and regulates chMDA5 in chicken cells is unclear. Thus, we measured the expression of chMDA5 in IBDV-infected DT40 cells and found it significantly increased. Overexpression of chMDA5 activated the IFN-β and Mx promoters via IRF7-dependent pathways and inhibited replication of IBDV in DT40 cells. The opposite effect occurred after chMDA5 knockdown using siRNA. Also, gga-miR-142-5p regulated chMDA5 according to bioinformatic analysis and data from a dual-luciferase reporter system. Overexpression of gga-miR-142-5p reduced the expression of the chMDA5 protein, promoting IBDV replication, and decreased the activity of the IFN-β and Mx promoters via an IRF7-dependent pathway; however, it had no effect on the NF-κB-dependent pathway in DT40 cells. Thus, gga-miR-142-5p is a negative regulator of chMDA5 and promotes IBDV replication in DT40 cells through an IRF7-dependent pathway.