Evolutional conservation of cytosolic antiviral activity with type I interferon mediated by the retinoic acid-inducible gene I-like receptor pathway in teleosts (170.11)

Abstract

Abstract The retinoic acid-inducible gene-I-like receptor (RLR) family, one of the pattern recognition receptors (PRRs), is important for the cytosolic immune response to recognize viral RNAs as pathogen-associated molecular patterns (PAMPs). RLR family members MDA5 (melanoma differentiation-associated gene 5) and LGP2 (laboratory of genetics and physiology 2) enhance gene expression of type-I interferon (IFN-I) and inflammatory cytokines through the IPS-1 (mitochondrial adaptor IFN-β promoter stimulator-1) cascade. In this study, MDA5, LGP2 and IPS-1 were cloned from the kidney of the Japanese flounder, Paralichthys olivaceus, and their phylogenetic analyses showed their conservation to those of higher vertebrates. MDA5 and LGP2 mRNA expression were strongly up-regulated by poly I:C stimulation or VHSV infection, whereas IPS-1 mRNA expression was not. To reveal the antiviral activity of these molecules, expression vectors were constructed and used in an antiviral assay against VHSV and HIRRV using the HINAE (Hirame natural embryonic) cell line. Viral replications were visibly repressed by overexpression of the MDA5, LGP2 and IPS-1 genes. The antiviral activities were attributed to the up-regulation of type I interferon (IFN) and IFN-inducible genes (Mx and ISG15). These results indicate that MDA5, LGP2 and IPS-1 are capable of causing the inhibition of viral replication through the induction of type I IFN and IFN-inducible genes.