Chen Shu-O, Fang Shih-Hua, Shih Dien-Yun, Chang Tien-Jye, Liu Jau-Jin
Department of Veterinary, College of Veterinary Medicine, National Chung-Hsing University, Taichung, 402, Taiwan.
Virus Genes. 2009 Feb;38(1):10-8. doi: 10.1007/s11262-008-0299-9. Epub 2008 Nov 14.
Nitric oxide (NO) has been shown to suppress Japanese encephalitis virus (JEV) RNA synthesis, viral protein accumulation, and virus release from infected cells. In this article, the potential viral structural proteins as the activators of NO product were studied at the molecular level. First, the genomic region encoding the JEV structural proteins was cloned into a prokaryotic expression vector pET for high-level expression. After purification, these JEV recombinant proteins were added to macrophages to examine the productions of NO and pro-inflammatory mediators. In this study, the recombinant core protein, but not envelope (E), could trigger NO and pro-inflammatory mediators (TNF-alpha, IL-6, and IL-12) productions on macrophages. And their effects were about 85-95% relative to LPS-stimulated macrophages in a dose-dependent manner. Meanwhile, the rCore-2D could up regulate promoters of IL-8 and TNF-alpha via EGFP expression in reporter plasmid (IL-8p-EGFP and TNF-alphap-EGFP)-transfected cells by flow cytometric analysis. These results suggest that JEV core protein could regulate pro-inflammatory mediators and NO production, and may play a crucial role in the innate immunity for the host to restrict the initial stage of JEV infection.
一氧化氮(NO)已被证明可抑制日本脑炎病毒(JEV)的RNA合成、病毒蛋白积累以及病毒从感染细胞中的释放。在本文中,在分子水平上研究了作为NO产物激活剂的潜在病毒结构蛋白。首先,将编码JEV结构蛋白的基因组区域克隆到原核表达载体pET中进行高水平表达。纯化后,将这些JEV重组蛋白添加到巨噬细胞中,以检测NO和促炎介质的产生。在本研究中,重组核心蛋白而非包膜(E)蛋白可触发巨噬细胞产生NO和促炎介质(TNF-α、IL-6和IL-12)。并且它们的作用相对于LPS刺激的巨噬细胞约为85-95%,呈剂量依赖性。同时,通过流式细胞术分析,rCore-2D可在报告质粒(IL-8p-EGFP和TNF-alphap-EGFP)转染的细胞中通过EGFP表达上调IL-8和TNF-α的启动子。这些结果表明,JEV核心蛋白可调节促炎介质和NO的产生,并且可能在宿主限制JEV感染初始阶段的固有免疫中起关键作用。