摘要：SummaryIn mammals, LGP2 is the enigmatic RLR family member, being initially believed as an inhibitor of RLR-triggered IFN response but subsequently as an activator of MDA5 signaling and an inhibitor of RIG-I signaling. The contradiction happens to fish LGP2. Here, we generate algp2loss-of-function (lgp2lof/lof) zebrafish mutant, which is highly susceptible to SVCV infection, displaying an initially decreased activation of IFN response and a following increased one. Mechanistically, zebrafish LGP2 functions as the essential activator of IFN response dependent on MDA5 at the early stage of viral infection but as a negative regulator by impairing mRNA levels oftbk1andikkiat the late stage of viral infection. The function switch of LGP2 is related to cellular IFN production during viral infection. Our data demonstrate that zebrafish LGP2 is a key homeostatic regulator of IFN response and thus essential for zebrafish survival against SVCV infection.Graphical abstractDisplay OmittedHighlights•Zebrafish LGP2 is crucial for host survival through initiating IFN response•Zebrafish LGP2 exerts dual regulation of IFN response during SVCV infection•The function switch of zebrafish LGP2 is related to cellular IFN productionBiochemistry; Immunology; Virology;
