Nuclear scaffold attachment factor A functions as a potential viral recognition receptor involved in the antiviral immunity of grass carp (Ctenopharyngodon idella).

As one of the most primitive vertebrates, fish have evolved a distinct repertoire of viral recognition receptors. However, the existence of nuclear viral recognition receptors in fish remains uncertain. In this study, we identified a scaffold attachment factor A (SAFA), CiSAFA, as a potential nuclear recognition receptor for grass carp reovirus (GCRV) in grass carp (Ctenopharyngodon idella). CiSAFA shares high amino acid sequence similarity (70.3-99.6 %) and identity (56.1-98.6 %) with its counterparts from other vertebrates and contains three conserved domains, namely, SAP, SPRY, and AAA_33. On the basis of the subcellular location analysis, CiSAFA was found to localize to the nucleus. In vitro, CiSAFA can bind to poly(I:C) and induce interferon (IFN) expression. The expression data revealed that CiSAFA exhibited ubiquitous mRNA expression across all the tissues of grass carp. After GCRV infection, CiSAFA showed significantly upregulated mRNA expression levels and exhibited an expression pattern similar to that of IFN1 in the spleen and head kidney. The results of RNA immunoprecipitation indicated that CiSAFA might interact with dsRNA segment 6 of GCRV. The overexpression of CiSAFA significantly increased the expression levels of several representative antiviral genes, including interferon regulatory factor 3 (IRF3), IRF7, IFN1, and virus-induced gene 1 (GIG1), and inhibited GCRV replication. To our knowledge, this study represents the first discovery of a potential nuclear recognition receptor, CiSAFA, for GCRV in grass carp and reveals its antiviral immune mechanism against GCRV infection, which may provide new insight into host immune recognition system-virus interactions in fish.