FTR67, a member of the fish-specific finTRIM family, triggers IFN pathway and against spring viremia of carp virus.

Tripartite motif (TRIM) proteins have attracted particular research interest because of their multiple functions in the antiviral innate immune response. TRIM proteins perform different functions during virus infection, some play a role in inhibiting while others play a role in promoting. In this study, we described a species-specific TRIM gene named ftr67. Analysis of tissue distribution showed that ftr67 was mainly expressed in the gill and liver in five examined tissues of zebrafish. The phylogenic analysis showed that ftr67 was closest to the grass carp TRIM67. Overexpression of ftr67 resulted in a significantly decreased SVCV entry and impaired SVCV replication in FHM cells. Furthermore, overexpression of ftr67 could significantly induce the upregulation of molecular sensor RIG-I, IRF3/7, IFN and ISGs. In addition, RING domain of ftr67 was a required part essential for the antiviral effect. In summary, our results demonstrated that the important role of ftr67 in regulating SVCV infection, which offers a potential target for development of anti-SVCV therapies.

Zebrafish NIK Mediates IFN Induction by Regulating Activation of IRF3 and NF-κB.

Type I IFN mediates the innate immune system to provide defense against viral infections. NF-κB-inducing kinase (NIK) potentiates the basal activation of endogenous STING, which facilitates the recruitment of TBK1 with the ectopically expressed IRF3 to induce IFN production. Moreover, NIK phosphorylates IKKα and confers its ability to phosphorylate p100 (also known as NF-κB2) in mammals. Our study demonstrated that NIK plays a critical role in IFN production in teleost fish. It was found that NIK interacts with IKKα in the cytoplasm and that IKKα phosphorylates the NIK at the residue Thr432, which is different from the mammals. Overexpression of NIK caused the activation of IRF3 and NF-κB, which in turn led to the production of IFN and IFN-stimulated genes (ISGs). Furthermore, the ectopic expression of NIK was observed to be associated with a reduced replication of the fish virus, whereas silencing of endogenous NIK had an opposite effect in vitro. Furthermore, NIK knockdown significantly reduced the expression of IFN and key ISGs in zebrafish larvae after spring viremia of carp virus infection. Additionally, the replication of spring viremia of carp virus was enhanced in NIK knockdown zebrafish larvae, leading to a lower survival rate. In summary, our findings revealed a previously undescribed function of NIK in activating IFN and ISGs as a host antiviral response. These findings may facilitate the establishment of antiviral therapy to combat fish viruses.

Fish-specific finTRIM FTR36 triggers IFN pathway and mediates inhibition of viral replication.

The 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 finTRIM FTR36, which can activate IFN-pathways and stimulate ISGs to provide host defense against viral infections.