Viral resistance and interferon signalling in Signal transducer and Activator of Transcription (STAT)-2 knockout fish cells. Oncorhynchus tshawytscha strain:CHSE-214 cell line

Interferons (IFN) belong to a group of cytokines specialised in the immunity to viruses. Upon viral infection, type I IFN are produced and alter the transcriptome of responding cells through induction of a set of Interferon Stimulated Genes (ISGs) with regulatory or antiviral function, resulting in a cellular antiviral state. Fish genomes have both type I IFNs and type II IFN (IFNγ), but no type III (λ) IFN has been identified. Their receptors are not simple counterparts of the mammalian type I/II IFN receptors, since alternative chains are used in type I IFN receptors. The mechanisms of the downstream signalling remains partly undefined. In mammals, members of the Signal Transducer and Activator of family of transcription factors are responsible for the transmission of the signal from cytokine receptors, and STAT2 is required for type I but not type II IFN signalling. In fish, its role in IFN signalling in fish remains unclear. We isolated a chinook cell line, GS2, with a STAT2 gene knocked out by CRISPR/Cas9 genome editing. In this cell line, the induction of ISGs by stimulation with a recombinant type I IFN is completely obliterated as evidenced by comparative RNA-seq analysis of the transcriptome of GS2 and its wild type counterpart, EC. Despite a complete absence of ISGs induction, the GS2 cell line has a remarkable ability to resist to viral infections. Therefore, other STAT2-independent pathways may be induced by the viral infection, illustrating the robustness and possible redundancy of the innate antiviral defences in fish.