Zheng Jiaying, Chen Haotian, Liu Qiting, Lin Feifei, Guo Xixi, Huang Xiaohong, Qin Qiwei, Huang Youhua
College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China; Nansha-South China Agricultural University Fishery Research Institute, Guangzhou, China.
College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China.
Fish Shellfish Immunol. 2025 Oct;165:110475. doi: 10.1016/j.fsi.2025.110475. Epub 2025 Jun 6.
Interleukin (IL) 15 and IL-15-like (IL-15L) are members of the cytokine receptor γ chain (γc) family proteins, which play critical roles in the growth, and differentiation of various cell lineages of the innate and adaptive immune systems. However, the functions of teleost IL-15L upon virus infection still remained unknown. In the current study, a homolog of IL-15L from grouper (Epinephelus coioides) was identified and characterized. Sequence analysis indicated that EcIL-15L contained a conserved IL-15 domain (aa 13-134). Quantitative Reverse Transcription PCR (qRT-PCR) analysis indicated that the expression level of EcIL-15L was markedly increased upon Singapore grouper iridovirus (SGIV) infection, indicating that EcIL-15L may be involved in the host's defense against infections by fish viruses. In addition, EcIL-15L mostly colocalized with endoplasmic reticulum, and partially colocalized with the Golgi apparatus. EcIL-15L overexpression significantly decreased SGIV replication, as demonstrated by a reduce in viral gene transcriptions and protein synthesis. In contrast, the replication of SGIV was promoted by the knockdown of EcIL-15L in grouper cells. Furthermore, compared to SGIV subunit vaccine alone, the combination of vaccine and EcIL-15L significantly improved the relative protective effect against SGIV. Meanwhile, the combination of EcIL-15L significantly increased the specific antibody titer in serum or the transcription levels of immune related genes in vivo, respectively. In conclusion, our findings indicated that EcIL-15L exerted antiviral function against SGIV, and acted as a cytokine adjuvant to improve protective effects induced by SGIV subunit vaccine.
白细胞介素（IL）-15和IL-15样分子（IL-15L）是细胞因子受体γ链（γc）家族蛋白成员，在天然免疫和适应性免疫系统的各种细胞谱系的生长和分化中起关键作用。然而，硬骨鱼IL-15L在病毒感染时的功能仍不清楚。在本研究中，鉴定并表征了来自石斑鱼（Epinephelus coioides）的IL-15L同源物。序列分析表明，石斑鱼IL-15L（EcIL-15L）含有一个保守的IL-15结构域（第13至134位氨基酸）。定量逆转录PCR（qRT-PCR）分析表明，在新加坡石斑鱼虹彩病毒（SGIV）感染后，EcIL-15L的表达水平显著升高，表明EcIL-15L可能参与宿主对鱼类病毒感染的防御。此外，EcIL-15L大多与内质网共定位，部分与高尔基体共定位。EcIL-15L的过表达显著降低了SGIV的复制，病毒基因转录和蛋白质合成减少证明了这一点。相反，在石斑鱼细胞中敲低EcIL-15L可促进SGIV的复制。此外，与单独的SGIV亚单位疫苗相比，疫苗与EcIL-15L的组合显著提高了对SGIV的相对保护效果。同时，EcIL-15L的组合分别显著提高了血清中的特异性抗体滴度或体内免疫相关基因的转录水平。总之，我们的研究结果表明，EcIL-15L对SGIV具有抗病毒功能，并作为细胞因子佐剂提高了SGIV亚单位疫苗诱导的保护效果。
