Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China.
Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China.
Fish Shellfish Immunol. 2022 Nov;130:380-390. doi: 10.1016/j.fsi.2022.09.043. Epub 2022 Sep 21.
Transcription factor ATF1 is a member of the ATF/CREB family of the CREB subfamily and is involved in physiological processes such as tumorigenesis, organ development, reproduction, cell survival, and apoptosis in mammals. However, studies on ATF1 in fish have been relatively poorly reported, especially on its role in antiviral immunity in fish. In this study, ATF1 from orange-spotted grouper (named EcATF1) were cloned and characterized. Molecular characterization analysis showed that EcATF1 encodes a 307-amino-acid protein, containing PKID and bZIP_CREB1 domains. Homology analysis showed that had the highest homology with E. lanceolatus(88.93%). Tissue expression pattern showed that EcATF1 was extensively distributed in twelve selected tissues, with higher expression in the skin, gill, liver and spleen. Subcellular localization analysis showed that EcATF1 was distributed in the nucleus of GS cells. EcATF1 overexpression inhibits Singapore grouper iridovirus (SGIV) and red-spotted grouper nervous necrosis virus (RGNNV) replication, as evidenced by a diminished degree of CPE induced by SGIV and RGNNV and a reduction in the level of viral gene transcription and viral capsid protein expression. Furthermore, EcATF1 overexpression upregulated interferon pathway-related genes and proinflammatory factors, and increased the promoter activities of IFN, IFN stimulated response element (ISRE), and nuclear factor κB(NFκB). Meanwhile, EcATF1 overexpression positive regulate the MHC-I signaling pathway, and upregulated the promoter activity of MHC-I. Collectively, these data demonstrate that EcATF1 plays an important role during the host antiviral immune response. This study provides insights into the function of ATF1 in the immune system of lower vertebrates.
转录因子 ATF1 是 CREB 亚家族的 ATF/CREB 家族的成员，参与哺乳动物的肿瘤发生、器官发育、繁殖、细胞存活和细胞凋亡等生理过程。然而，鱼类中 ATF1 的研究报道相对较少，特别是其在鱼类抗病毒免疫中的作用。本研究克隆和鉴定了卵形鲷（EcATF1）的 ATF1。分子特征分析表明，EcATF1 编码一个 307 个氨基酸的蛋白，包含 PKID 和 bZIP_CREB1 结构域。同源性分析表明，与 E. lanceolatus 的同源性最高（88.93%）。组织表达模式显示 EcATF1 在 12 种选定的组织中广泛分布，在皮肤、鳃、肝和脾中表达水平较高。亚细胞定位分析表明 EcATF1 分布在 GS 细胞的细胞核中。EcATF1 的过表达抑制了新加坡石斑鱼虹彩病毒（SGIV）和红鳍东方鲀神经坏死病毒（RGNNV）的复制，这表现在 SGIV 和 RGNNV 诱导的 CPE 程度降低以及病毒基因转录和病毒衣壳蛋白表达水平降低。此外，EcATF1 的过表达上调了干扰素通路相关基因和促炎因子的表达，增强了 IFN、ISRE 和 NFκB 的启动子活性。同时，EcATF1 的过表达正向调节 MHC-I 信号通路，并上调 MHC-I 的启动子活性。综上所述，这些数据表明 EcATF1 在宿主抗病毒免疫反应中发挥重要作用。本研究为 ATF1 在低等脊椎动物免疫系统中的功能提供了新的见解。
