Rahal Elias A, Hajjar Helene, Rajeh Mirna, Yamout Bassem, Abdelnoor Alexander M
1Department of Experimental Pathology, Immunology, and Microbiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
2Department of Neurology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Viral Immunol. 2015 Jun;28(5):297-302. doi: 10.1089/vim.2014.0129. Epub 2015 Apr 14.
Several studies have shown a potential association between the Herpesviridae members, the Epstein-Barr virus (EBV) and Human herpes virus 6 (HHV-6), and an increased risk of autoimmune disease development. Because of the ability of these viruses to cause recurrent infections, various viral antigens, including viral DNA, are consistently shed. These antigens may then play a role in triggering autoimmune processes or contributing to autoimmune mechanisms. Therefore, this study examined whether the DNA of EBV or that of HHV-6A is capable of triggering IL-17, the autoimmune-associated cytokine, in mice. BALB/c mice were intraperitoneally injected with various copy numbers of either EBV or HHV-6A DNA. One group was injected with sterile water (the DNA solvent), and another was left uninjected. A mouse group that was administered DNA obtained from Staphylococcus epidermidis was included to ensure that any observed effects would pertain to the viral DNA tested. Mice were sacrificed and their sera were examined using an enzyme-linked immunosorbent assay for IL-17 and IL-23, as pro-autoimmune cytokines, IL-10, as an anti-inflammatory cytokine, and IFN-γ, as a pro-inflammatory cytokine, on days 3, 6, and 9 post-injection. All mouse groups injected with different copy numbers of EBV DNA or HHV-6A DNA displayed higher IL-17 levels than did the group injected with water on days 3, 6, and 9 post-injection. The highest IL-17 levels appeared to coincide with a marked increase in IL-23 and a decrease in IL-10 levels. Unlike the S. epidermidis DNA, which increased IFN-γ levels but not IL-17 or IL-23 levels, the viral DNA tested increased all three mediators, indicating that triggering Th17 responses is a specific property of EBV and HHV-6A DNA. In conclusion, EBV and HHV-6A viral DNA are capable of enhancing the production of the pro-inflammatory cytokine IL-17, which has been shown to play a role in autoimmune diseases.
多项研究表明，疱疹病毒科成员、爱泼斯坦-巴尔病毒（EBV）和人类疱疹病毒6型（HHV-6）与自身免疫性疾病发生风险增加之间可能存在关联。由于这些病毒具有引起反复感染的能力，包括病毒DNA在内的各种病毒抗原会持续释放。这些抗原可能在触发自身免疫过程或促成自身免疫机制方面发挥作用。因此，本研究检测了EBV或HHV-6A的DNA是否能够在小鼠体内触发白细胞介素-17（IL-17），这是一种与自身免疫相关的细胞因子。将不同拷贝数的EBV或HHV-6A DNA腹腔注射到BALB/c小鼠体内。一组注射无菌水（DNA溶剂），另一组不进行注射。纳入一组注射从表皮葡萄球菌获得的DNA的小鼠，以确保观察到的任何效应都与所测试的病毒DNA有关。在注射后第3天、第6天和第9天，处死小鼠并使用酶联免疫吸附测定法检测其血清中的IL-17和IL-23（作为促自身免疫细胞因子）、IL-10（作为抗炎细胞因子）以及IFN-γ（作为促炎细胞因子）。在注射后第3天、第6天和第9天，所有注射不同拷贝数EBV DNA或HHV-6A DNA的小鼠组的IL-17水平均高于注射水的组。IL-17的最高水平似乎与IL-23的显著增加和IL-10水平的降低同时出现。与表皮葡萄球菌DNA不同，后者增加了IFN-γ水平，但未增加IL-17或IL-23水平，所测试的病毒DNA增加了所有这三种介质，表明触发Th17反应是EBV和HHV-6A DNA的一个特性。总之，EBV和HHV-6A病毒DNA能够增强促炎细胞因子IL-17的产生，IL-17已被证明在自身免疫性疾病中起作用。
