SVCV infection triggers fish IFN response through RLR signaling pathway

Abstract

In mammals, virus infection of host cells triggers innate immune response, characterized by induction of interferon (IFN) and downstream IFN-stimulated genes (ISGs). The initiation of IFN antiviral response is dependent on host recognition of virus infection. In fish, similar IFN antiviral response is induced in response to RNA or DNA virus infection; however, the detailed mechanisms underlying recognition of a given virus and activation of downstream signaling remain largely unexplored. Using an infection model with Epithelioma papulosum cyprini (EPC) cells and spring viremia of carp virus (SVCV), a negative sense single-stranded RNA virus, we reported that fish RLR signaling pathway was involved in SVCV-triggered fish IFN response. IFN response was significantly initiated in EPC cells when infected with SVCV, as evidenced by activation of fish IFN promoters, upregulation of IFN and ISGs at mRNA and protein levels. However, function blockade of RIG-I and MDA5, two cytosolic receptors of fish RLR family, significantly attenuated the activation of fish IFN promoters and also the induction of fish IFN and ISGs by SVCV infection. Consistently, SVCV infection-triggered IFN response were blocked in EPC cells when transfected with the dominant negative mutants of pivotal RLR signaling factors, including MAVS, MITA, TBK1, IRF3 and IRF7. These results together shed light on the conservation of RLR-mediated IFN signaling that contributes to fish cells responding to RNA virus infection.