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虹鳟鱼(Oncorhynchus mykiss)抗病毒免疫中 TRIM32 的分子机制。

Molecular mechanism of TRIM32 in antiviral immunity in rainbow trout (Oncorhynchus mykiss).

机构信息

College of Animal Science and Technology, Northeast Agicultural University, Harbin, 150030, China.

College of Animal Science and Technology, Northeast Agicultural University, Harbin, 150030, China.

出版信息

Fish Shellfish Immunol. 2024 Oct;153:109765. doi: 10.1016/j.fsi.2024.109765. Epub 2024 Jul 14.

DOI:10.1016/j.fsi.2024.109765
PMID:39004296
Abstract

TRIM family proteins are widely found in multicellular organisms and are involved in a wide range of life activities, and also act as crucial regulators in the antiviral natural immune response. This study aimed to reveal the molecular mechanism of rainbow trout TRIM protein in the anti-IHNV process. The results demonstrated that 99.1 % homology between the rainbow trout and the chinook salmon (Oncorhynchus tshawytscha) TRIM32. When rainbow trout were infected with IHNV, the TRIM32 was highly expressed in the gill, spleen, kidney and blood. Meanwhile, rainbow trout TRIM32 has E3 ubiquitin ligase activity and undergoes K29-linked polyubiquitination modifications dependent on the RING structural domain was determined by immunoprecipitation. TRIM32 could interact with the NV protein of IHNV and degrade NV protein through the ubiquitin-proteasome pathway, and was also able to activate NF-κB transcription, thereby inhibiting the replication of IHNV. Moreover, the results of the animal studies showed that the survival rate of rainbow trout overexpressing TRIM32 was 70.2 % which was significantly higher than that of the control group, and stimulating the body to produce high levels of IgM when the host was infected with the virus. In addition, TRIM32 can activate the NF-κB signalling pathway and participate in the antiviral natural immune response. The results of this study will help us to understand the molecular mechanism of TRIM protein resistance in rainbow trout, and provide new ideas for disease resistance breeding, vaccine development and immune formulation development in rainbow trout.

摘要

TRIM 家族蛋白广泛存在于多细胞生物中,参与多种生命活动,也是抗病毒天然免疫反应中的关键调节因子。本研究旨在揭示虹鳟 TRIM 蛋白在抗 IHNV 过程中的分子机制。结果表明,虹鳟与奇努克三文鱼(Oncorhynchus tshawytscha)TRIM32 的同源性为 99.1%。当虹鳟感染 IHNV 时,TRIM32 在鳃、脾、肾和血液中高度表达。同时,虹鳟 TRIM32 具有 E3 泛素连接酶活性,并通过免疫沉淀确定其 RING 结构域依赖性的 K29 连接多泛素化修饰。TRIM32 可以与 IHNV 的 NV 蛋白相互作用,并通过泛素蛋白酶体途径降解 NV 蛋白,还可以激活 NF-κB 转录,从而抑制 IHNV 的复制。此外,动物研究的结果表明,过表达 TRIM32 的虹鳟的存活率为 70.2%,明显高于对照组,并且在宿主感染病毒时可以刺激机体产生高水平的 IgM。此外,TRIM32 可以激活 NF-κB 信号通路并参与抗病毒天然免疫反应。本研究的结果将有助于我们了解虹鳟 TRIM 蛋白抵抗的分子机制,并为虹鳟的抗病育种、疫苗开发和免疫制剂开发提供新的思路。

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