Study On The Mechanism Of Zebrafish FTR36 And NIK Inhibiting SVCV Replication

Aquatic diseases are the main factors restricting the development of aquatic industry.Spring viremia of carp virus(SVCV)is a single strand RNA(ss RNA)virus and it is the causative agent of spring viremia of carp(SVC),is characterized by acute bleeding and highly contagious.It is a serious disease responsible for high mortality and severe losses of cultured common carp.Some host proteins play important roles against viral infections,what role does the zebrafish FTR36 and NIK play in the fight against viral diseases such as SVCV,and through which mechanism remains to be studied.This experiment starts with the affection of fish host protein(FTR36 and NIK)and SVCV,in order to explore the relationship between zebrafish host protein(FTR36 and NIK)and SVCV from the perspective of natural immunity,and reveal its mechanism of action,which is the related prevention and control technology of SVCV.These research and development of products provide a certain scientific and theoretical basis.The main contents of this study are as follows:1.Study on the mechanism of FTR36 inhibiting SVCV replicationThe tripartite motif(TRIM)family involves many cellular processes,including fundamental functions in antiviral immunity.Antiviral activities of TRIMs are reported in a variety of patterns,and one of the most significant channels is related to the activation of the type-I interferon(IFN)pathway.In this study,we described a fintrim(ftr)gene named ftr36,which is mainly expressed in the gills,skin,and intestines.This study shows that ftr36 encodes a protein affording a potent antiviral effect.In vitro,overexpression of FTR36 mediated an upregulated pattern of recognition receptor retinoic acid–inducible gene I(RIG-I),interferon regulatory factor 3/7(IRF3/7),IFN,and IFN-stimulated genes(ISGs)expression.Thereby,FTR36 expression could afford host defense against the spring viremia of carp virus(SVCV)and the giant salamander iridovirus(GSIV).With the deletion of the RING domain or B30.2 domain separately,the antiviral ability of FTR36 was abolished partially and almost lost its ability to activate the IFN-pathway.These findings indicate that both RING and B30.2 domains are indispensable for the antiviral activity of FTR36.Altogether,this study described a fin TRIM FTR36,which can activate IFN-pathways and stimulate ISGs to provide host defense against viral infections.2.Study on the mechanism of NIK inhibiting SVCV replicationNuclear factor(NF)-kB inducing kinase(NIK)was reported to potentiate the basal activation of endogenous STING,which facilitates the recruitment of TBK1 with the ectopically expressed IRF3 to induce IFN production.Moreover,NIK phosphorylates IKKa and confers its ability to phosphorylate p100(aka NF-kB2)in mammals.Our study described NIK plays a critical role in IFN production in teleost fish.NIK interacts with IKKa in cytoplasm and IKKa phosphorylates NIK at Thr-432,which is different from mammals.Overexpressing NIK activates NF-kB and IRF3,which lead to the production of IFNs.NIK responds to ds DNA,ds RNA and ss RNA viral infection.In addition,overexpressing NIK in FHM cells inhibited SVCV replication while knocking down endogenous NIK fostered the viral infection.In summary,our findings reveal previously undescribed functions of NIK in activating IFNs for host antiviral response.