Functions of the two zebrafish MAVS variants are opposite in the induction of IFN1 by targeting IRF7.

Abstract

IFNs create the first line of host cells to defense viral infection, however, unrestricted expression of IFN can be hazardous to the host. IRF7 is the master regulator of type I IFN expression. To our knowledge, non research about the inhibition of IFN expression by targeting IRF7 has been reported in fish. In this study, we reported that the splicing variant of wildtype MAVS (MAVS_tv1), MAVS_tv2, negatively regulated IRF7-mediated IFN production. Firstly, in vivo, the transcriptional levels of MAVS_tv2 in trunk kidney and spleen from the zebrafish infected with SVCV were monitored. Then, in vitro, the protein expression pattern of MAVS_tv2 in zebrafish cell lines was detected using anti-MAVS_tv2 antibody. Furthermore, overexpression of MAVS_tv2 decreased the activation of IFN1 promoter that induced by IRF7 in a dose-dependent manner, whereas it had little effect on IRF3, a close relative of IRF7. In addition, such inhibition was also observed in IRF7-mediated epcIFN promoter and ISRE activities, but not in the activation of the promoters of type II IFNs and NF-ĸB, due to IRF7 not regulating their expression. Lastly, overexpression of MAVS_tv2 decreased the transcriptional levels of several IFN-stimulated genes activated by IRF7. These findings suggest that MAVS_tv2 is a negative regulator of IFN1 by targeting IRF7.