Zhang Luhao, Kang Shaozhu, Chen Hong, Liao Jiaming, Sun Mengshi, Wu Siting, Xu Zhuqing, Xu Linting, Zhang Xin, Qin Qiwei, Wei Jingguang
University Joint Laboratory of Guangdong Province, Hong Kong and Macao Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, PR China.
University Joint Laboratory of Guangdong Province, Hong Kong and Macao Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, PR China; Guangdong Laboratory for Lingnan Modern Agriculture, PR China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266000, PR China; Southern Marine Science and Engineering Guangdong Laboratory, Zhuhai, 528478, China.
Fish Shellfish Immunol. 2022 May;124:164-173. doi: 10.1016/j.fsi.2022.04.006. Epub 2022 Apr 6.
Transforming growth factor-β activated kinase 1 (TAK1) is a member of the mitogen-activated protein kinase family. It is an upstream factor of the IκB kinase, which activates IKKα and IKKβ. TAK1 is a key factor in the induction of nuclear factor κB (NF-κB) and plays a crucial role in the activation of inflammatory responses. However, the roles of TAK1 during viral infection in teleost fish are largely unknown. In this study, we cloned a TAK1 homolog (HgTAK1) from the hybrid grouper (Epinephelus fuscoguttatus♂ × Epinephelus lanceolatus♀). The open reading frame of HgTAK1 consists of 1728 nucleotides encoding 575 amino acids, and the predicted molecular weight is 64.32 kDa HgTAK1 has an S_TKc domain, which consists of a serine/threonine protein kinase and a catalytic domain. Expression pattern analysis showed that HgTAK1 was distributed in all tested tissues, with abundant contents in the heart, head kidney, and blood. Additionally, HgTAK1 was distributed in the cytoplasm of grouper spleen (GS) cells. After Singapore grouper iridovirus (SGIV) infection, the expression of HgTAK1 increased in GS cells. Overexpression of HgTAK1 could promote the replication of SGIV in GS cells and inhibit the activation of NF-κB and IFN stimulated response elements (ISRE) in reporter assay. When co-expressed with IRF3 or HgIRF7 in GS cells, HgTAK1 obviously down-regulated IRF3- or IRF7-mediated the NF-κB and ISRE promoter induction. The interaction between HgTAK1 and IRF3 or IRF7 has been identified by co-immunoprecipitation assay. These findings provide a basis for understanding the innate immune mechanism of the grouper response to viral infection.
转化生长因子-β激活激酶1（TAK1）是丝裂原活化蛋白激酶家族的成员。它是IκB激酶的上游因子，可激活IKKα和IKKβ。TAK1是诱导核因子κB（NF-κB）的关键因子，在炎症反应激活中起关键作用。然而，TAK1在硬骨鱼病毒感染过程中的作用在很大程度上尚不清楚。在本研究中，我们从杂交石斑鱼（斜带石斑鱼♂×鞍带石斑鱼♀）中克隆了一个TAK1同源物（HgTAK1）。HgTAK1的开放阅读框由1728个核苷酸组成，编码575个氨基酸，预测分子量为64.32 kDa。HgTAK1具有一个S_TKc结构域，该结构域由丝氨酸/苏氨酸蛋白激酶和催化结构域组成。表达模式分析表明，HgTAK1分布于所有检测组织中，在心脏、头肾和血液中含量丰富。此外，HgTAK1分布于石斑鱼脾脏（GS）细胞的细胞质中。新加坡石斑鱼虹彩病毒（SGIV）感染后，GS细胞中HgTAK1的表达增加。HgTAK1的过表达可促进SGIV在GS细胞中的复制，并在报告基因检测中抑制NF-κB和干扰素刺激反应元件（ISRE）的激活。当在GS细胞中与IRF3或HgIRF7共表达时，HgTAK1明显下调IRF3或IRF7介导的NF-κB和ISRE启动子诱导。通过免疫共沉淀试验鉴定了HgTAK1与IRF3或IRF7之间的相互作用。这些发现为理解石斑鱼对病毒感染的先天免疫机制提供了依据。
