In mammals, tripartite motif (TRIM)-containing proteins are involved in interferon (IFN)-mediated antiviral response as pivotal players endowed with antiviral effects and modulatory capacity. Teleost fish have a unique subfamily of TRIM, called finTRIM (fish novel TRIM, FTR) generated by genus- or species-specific duplication of TRIM genes. Herein, four TRIM genes are identified from Epithelioma papulosum cyprini (EPC) cells, and phylogenetically close to the members of finTRIM, thus named FTREPC1, FTREPC2, FTREPC3 and FTREPC4. Despite high similarity in nucleotide sequence, FTREPC1/2 genes encode two proteins with a typically consecutive tripartite motif followed by a C-terminal B30.2 domain, while FTREPC3/4-encoding proteins retain only a RING domain due to early termination of translation. They are induced by poly(I:C), GCRV and SVCV as IFN-stimulated genes (ISGs), and this induction is severely impaired by blockade of STAT1 pathway and is dependent on a typical ISRE motif within the 5′ untranslated regions (5′UTRs) of FTREPC1/2/3/4 genes. Whereas overexpression of FTREPC1/2/3/4 alone does not activate fish IFN promoters, overexpression of FTREPC1 or FTREPC2, rather than FTREPC3 and FTREPC4, significantly impairs intracellular poly(I:C)-triggered activation of fish IFN promoters. Consistently, FTREPC1/2 promote virus replication through negatively regulating IFN response. Our results provide evidence for the involvement of EPC finTRIM proteins in IFN antiviral response and insights into genus- or species-specific regulation of fish innate immune pathways.

在哺乳动物中，含有三联基序 (TRIM) 的蛋白质作为具有抗病毒作用和调节能力的关键参与者参与了干扰素 (IFN) 介导的抗病毒反应。硬骨鱼有一个独特的 TRIM 亚科，称为 finTRIM（鱼新型 TRIM，FTR），由 TRIM 基因的属或种特异性复制产生。在此，从cyprini 丘疹上皮瘤中鉴定出 4 个 TRIM 基因(EPC) 细胞，并且在系统发育上接近 finTRIM 的成员，因此命名为 FTREPC1、FTREPC2、FTREPC3 和 FTREPC4。尽管核苷酸序列具有高度相似性，但 FTREPC1/2 基因编码的两种蛋白质具有典型的连续三联基序，后跟 C 端 B30.2 结构域，而 FTREPC3/4 编码蛋白质由于翻译提前终止而仅保留 RING 结构域。它们由作为 IFN 刺激基因 (ISG) 的 poly(I:C)、GCRV 和 SVCV 诱导，这种诱导因 STAT1 通路的阻断而受到严重损害，并且依赖于 5' 非翻译区内的典型 ISRE 基序（5 'UTRs) 的 FTREPC1/2/3/4 基因。虽然单独过表达 FTREPC1/2/3/4 不会激活鱼的干扰素启动子，但过表达 FTREPC1 或 FTREPC2，而不是 FTREPC3 和 FTREPC4，会显着损害细胞内聚（I：C)-触发激活鱼干扰素启动子。一致地，FTREPC1/2 通过负调节 IFN 反应促进病毒复制。我们的研究结果为 EPC finTRIM 蛋白参与 IFN 抗病毒反应提供了证据，并提供了对鱼类先天免疫途径的属或种特异性调节的见解。