Wen Xiaozhi, Guan Lingfeng, Wang Liqun, Zhang Zihan, Wei Xinyan, Qin Qiwei, Wang Shaowen
College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China.
College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China; Nansha-South China Agricultural University Fishery Research Institute, Guangzhou, 511464, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China; Southern Marine Science and Engineering Guangdong Laboratory, Zhuhai, 519000, China.
Fish Shellfish Immunol. 2025 Oct;165:110479. doi: 10.1016/j.fsi.2025.110479. Epub 2025 Jun 4.
Ran is a small G-protein that acts as a "molecular switch" in nucleoplasmic transport regulating cellular activities. However, the functions of Ran in grouper and their effects on the viral infections are still unclear. In this study, we identified and characterized Ran in Epinephelus coioides (EcRan). EcRan encodes a 215 amino acid polypeptide containing key conserved domains including G1-G5 box and C terminal domains. EcRan was widely expressed in different tissues of healthy groupers, and showed obvious nucleus localization. Upon infection of Singapore grouper iridovirus (SGIV) or red spotted grouper nervous necrosis virus (RGNNV), EcRan transcript was significantly decreased. Moreover, overexpression of EcRan remarkably inhibited the replication of SGIV and RGNNV, whereas knockdown of EcRan notably promoted the replication of SGIV and RGNNV. In addition, overexpressed EcRan positively regulated the transcription of interferon (IFN)-related and inflammatory factors, including IFN regulatory factor 3 (IRF3), myxovirus resistance gene 1 (MXI), laboratory of genetics and physiology 2 (LGP2), tumor necrosis factor alpha (TNF-α), tumor necrosis factor receptor-associated factor 6 (TRAF6) and interleukin 8 (IL-8). The transcription of these immune genes was down regulated when EcRan transcription was inhibited by siRNA. Taken together, EcRan showed the antiviral effects against SGIV and RGNNV infections by positively regulating innate immune response.
Ran是一种小G蛋白，在核质运输中作为“分子开关”发挥作用，调节细胞活动。然而，Ran在石斑鱼中的功能及其对病毒感染的影响仍不清楚。在本研究中，我们鉴定并表征了斜带石斑鱼（EcRan）中的Ran。EcRan编码一个215个氨基酸的多肽，包含关键的保守结构域，包括G1-G5框和C末端结构域。EcRan在健康石斑鱼的不同组织中广泛表达，并表现出明显的核定位。在感染新加坡石斑鱼虹彩病毒（SGIV）或红斑石斑鱼神经坏死病毒（RGNNV）后，EcRan转录本显著降低。此外，EcRan的过表达显著抑制了SGIV和RGNNV的复制，而敲低EcRan则显著促进了SGIV和RGNNV的复制。此外，过表达的EcRan正向调节干扰素（IFN）相关和炎症因子的转录，包括IFN调节因子3（IRF3）、抗黏液病毒基因1（MXI）、遗传学和生理学实验室2（LGP2）、肿瘤坏死因子α（TNF-α）、肿瘤坏死因子受体相关因子6（TRAF6）和白细胞介素8（IL-8）。当EcRan转录被siRNA抑制时，这些免疫基因的转录下调。综上所述，EcRan通过正向调节先天免疫反应，对SGIV和RGNNV感染显示出抗病毒作用。
