State Key Laboratory of Freshwater Ecology and Biotechnology, And Key Laboratory of Aquaculture Disease Control, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei Province, 430072, China; Guangxi Engineering Research Center for Fishery Major Diseases Control and Efficient Healthy Breeding Industrial Technology (GERCFT), Guangxi Academy of Sciences, Nanning, Guangxi Zhuang Autonomous Region, 530001, China.
Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wudayuan First Road 8, Wuhan, Hubei Province, 430223, China.
Dev Comp Immunol. 2023 May;142:104671. doi: 10.1016/j.dci.2023.104671. Epub 2023 Feb 17.
In mammals, the tripartite motif (TRIM) proteins have been identified as critical factors involved in various cellular processes, including antiviral immunity. In teleost fish, a subfamily of fish-specific TRIM (finTRIM, FTR) has emerged in genus- or species-specific duplication. In this study, a finTRIM gene, called ftr33, was identified in zebrafish (Danio rerio), and phylogenic analysis revealed that FTR33 is closely related with zebrafish FTR14. The FTR33 protein contains all conservative domains reported in other finTRIMs. The ftr33 has a constitutive expression in embryos and in tissues/organs of adult fish, and its expression can be induced following spring viremia of carp virus (SVCV) infection and interferon (IFN) stimulation. The overexpression of FTR33 significantly downregulated the expression of type I IFNs and IFN-stimulated genes (ISGs) both in vitro and in vivo, respectively, leading to the increased replication of SVCV. It was also found that FTR33 interacted with melanoma differentiation associated gene 5 (MDA5) or mitochondrial anti-viral signaling protein (MAVS) to weaken the promoter activity of type I IFN. It is thus concluded that the FTR33, as an ISG, in zebrafish can negatively regulate IFN-mediated antiviral response.
在哺乳动物中，三联基序（TRIM）蛋白已被鉴定为参与多种细胞过程的关键因素，包括抗病毒免疫。在硬骨鱼中，出现了一个鱼类特异性 TRIM（finTRIM，FTR）亚家族，在属或种特异性重复中出现。在这项研究中，在斑马鱼（Danio rerio）中鉴定出一个 finTRIM 基因，称为 ftr33，系统发育分析表明 FTR33 与斑马鱼 FTR14 密切相关。FTR33 蛋白包含其他 finTRIM 报道的所有保守结构域。ftr33 在胚胎和成年鱼的组织/器官中具有组成型表达，其表达可在鲤鱼病毒性出血败血症病毒（SVCV）感染和干扰素（IFN）刺激后诱导。FTR33 的过表达显著下调了 SVCV 在体外和体内的 I 型 IFNs 和 IFN 刺激基因（ISGs）的表达，导致 SVCV 的复制增加。还发现 FTR33 与黑色素瘤分化相关基因 5（MDA5）或线粒体抗病毒信号蛋白（MAVS）相互作用，削弱 I 型 IFN 的启动子活性。因此，FTR33 作为一种 ISG，在斑马鱼中可以负调控 IFN 介导的抗病毒反应。
