Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of Fishery Drug Development, Ministry of Agriculture and Rural Affairs, Key Laboratory of Aquatic Animal Immune Technology, Guangdong Provinces, Guangzhou, 510380, China.
Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of Fishery Drug Development, Ministry of Agriculture and Rural Affairs, Key Laboratory of Aquatic Animal Immune Technology, Guangdong Provinces, Guangzhou, 510380, China.
Fish Shellfish Immunol. 2020 Jul;102:211-217. doi: 10.1016/j.fsi.2020.04.017. Epub 2020 Apr 13.
Epidermal growth factor receptor (EGFR) is a tyrosine kinase protein and plays a critical role in virus infection by modulating innate immunity. In this study, we cloned and sequenced the EGFR coding sequence of mandarin fish, designed as scEGFR, and explored its characteristics. scEGFR mRNA was widely expressed in the tested tissues of mandarin fish, and the higher mRNA levels were expressed in kidney and spleen. scEGFR expression was up-regulated in spleen and CPB cells at early stage of ISKNV and SCRV infection. Gefitinib (EGFR inhibitor) inhibited ISKNV and SCRV replication, and increased the expression of the interferon-stimulated genes (ISG). However the EGF (EGFR activator) promoted ISKNV and SCRV replication, and decreased the interferon-stimulated genes. Those results indicated that scEGFR and its signaling involved in ISKNV and SCRV infection, and EGFR activation negatively regulated the interferon response, providing a potential target for the development of new therapic strategy against ISKNV and SCRV.
表皮生长因子受体(EGFR)是一种酪氨酸激酶蛋白,通过调节先天免疫在病毒感染中发挥关键作用。在这项研究中,我们克隆并测序了鳜鱼的 EGFR 编码序列,设计为 scEGFR,并探索了其特征。scEGFR mRNA 在鳜鱼测试组织中广泛表达,在肾脏和脾脏中表达水平较高。在 ISKNV 和 SCRV 感染的早期,scEGFR 在脾脏和 CPB 细胞中的表达上调。吉非替尼(EGFR 抑制剂)抑制了 ISKNV 和 SCRV 的复制,并增加了干扰素刺激基因(ISG)的表达。然而,EGF(EGFR 激活剂)促进了 ISKNV 和 SCRV 的复制,并降低了干扰素刺激基因的表达。这些结果表明,scEGFR 及其信号通路参与了 ISKNV 和 SCRV 的感染,EGFR 的激活负调控了干扰素反应,为开发针对 ISKNV 和 SCRV 的新治疗策略提供了潜在的靶点。