Fish MAVS is involved in RLR pathway-mediated IFN response

Abstract

Mammalian mitochondrial antiviral signaling protein (MAVS) is an essential adapter involved in retinoic acid-inducible gene-I (RIG-I)-like receptor (RLR)-triggered interferon (IFN) antiviral immunity. Fish MAVS homologues have been identified in several fish species; however, the signaling pathway involving fish MAVS-mediated IFN response remains to be investigated. In the present study, we report identification of a fish MAVS orthologue from crucian carp Carassius auratus blastulae embryonic (CAB) cells and its function role in fish RLR signaling. Crucian carp MAVS is constitutively expressed in CAB cells and is not transcriptionally induced by cytosolic poly (I:C) and IFN. Overexpression of crucian carp MAVS results in activation of fish IFN promoter and ISRE-containing promoter as well as transcriptional expression of IFN and ISGs including PKR and Mx1, which is impaired by functional blockade of signaling molecules TBK1 and IRF3/7. Either cytosolic poly (I:C)-induced or RIG-I-induced IFN response is attenuated by functional blockade of crucian carp MAVS. These results together indicate that fish MAVS contributes to IFN antiviral immunity downstream of cytosolic poly (I:C) and RIG-I and upstream of TBK1 and IRF3/7. Moreover, we provide evidence that apart from crucian carp MAVS, crucian carp MITA is also involved in cytosolic poly (I:C)- and RIG-I-induced IFN response.