Given that zebrafish LGP2 promotes IFN response at the early stage of virus infection through MDA5 (36) and titration of poly(I:C) may be analogous to the intracellular concentrations of viral dsRNA at different stages of virus infection, our results provide in vitro evidences that LGP2 indeed plays a conserved dual function in fish cells and mammalian cells, as a activator of IFN response by promoting MDA5 signaling at the early stage of virus infection and an inhibitor by impairing RIG-I/MDA5 signaling at the late stage of virus infection. Here, RIGI is linked to viral infectious disease.