Jun (Jun proto-oncogene,AP-1 transcription factor subunit) is a subunit or subfamily member of the transcription factor AP-1 and play an important role in host immune response.To further understand the function of jun gene in natural antiviral immunity of fish,the Japanese medaka (Oryzias latipes) was selected as the research fish model,and the homozygous mutant with jun deletion were obtained by CRISPR/CAS9 system and exposed to nervous necrosis virus (NNV) infection.Based on the gene cloning,the open reading frame of the medaka jun is 921 bp encoding 306 amino acids,containing N terminal jun super family structure domain and C terminal bZIP family structure domain.The RNA expression was highly detected in all examined tissues including the eyes,brain,gill,heart,kidney,ovary,testis,liver,and spleen.The mutant jun-/- was reduced by 124 bp in the genome,leaving only 59 amino acids N-terminal sequences,and missing the Jun superfamily domain and bZIP domain.Antiviral experiments were then carried out on larval and adult fish of the mutant strain by administrating NNV.The results showed that the disease resistance of larval mutants was enhanced,and the relative content of virus in adult tissues including the eye,brain,gill and muscle were significantly lower than in the wild type.The expression of jun and interferon-related genes fosl1,tbk1and irf3 that was induced by NNV virus were detected by qRT-PCR.It was found that the expression of jun in the mutant was blocked compared to the wild type,the expression of fosl1 and tbk1 was differentially reduced,while the expression of irf3was significantly up-regulated,indicating that the inhibition of jun expression may promote the release of irf3.These results suggest that the jun mutant has the ability of virus tolerance,and jun may be a negative regulator of the antiviral signaling pathway.