Fu Feiyu, Shao Qi, Zhang Jianjian, Wang Jie, Wang Zhaofei, Ma Jingjiao, Yan Yaxian, Sun Jianhe, Cheng Yuqiang
Shanghai Key Laboratory of Veterinary Biotechnology, Key Laboratory of Urban Agriculture (South), Ministry of Agriculture, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China.
Front Microbiol. 2023 Sep 8;14:1232314. doi: 10.3389/fmicb.2023.1232314. eCollection 2023.
The ability of stimulator of interferon genes (STING) to activate interferon (IFN) responses during RNA virus infection has been demonstrated in different mammalian cells. Despite being the host of numerous RNA viruses, the role of STING in bats during RNA virus infection has not been elucidated. In this study, we identified and cloned the STING gene of the Brazilian free-tailed bat () and tested its ability to induce IFN-β by overexpressing and knocking down bat STING (BatSTING) in 1 lung (TB1 Lu) cells. In addition, we used green fluorescent protein (GFP)-labeled vesicular stomatitis virus (VSV) VSV-GFP as a model to detect the antiviral activity of BatSTING. The results showed that overexpression of STING in TB1 Lu cells stimulated by cGAS significantly inhibited RNA virus replication, and the antiviral activities were associated with its ability to regulate basal expression of IFN-β and some IFN stimulated genes (ISGs). We also found that BatSTING was able to be activated after stimulation by diverse RNA viruses. The results of TB1 Lu cells with STING deficiency showed that knockdown of BatSTING severely hindered the IFN-β response triggered by VSV-GFP. Based on this, we confirm that BatSTING is required to induce IFN-β expression during RNA virus infection. In conclusion, our experimental data clearly show that STING in bat hosts plays an irreplaceable role in mediating IFN-β responses and anti-RNA virus infection.
干扰素基因刺激物（STING）在RNA病毒感染期间激活干扰素（IFN）反应的能力已在不同的哺乳动物细胞中得到证实。尽管蝙蝠是众多RNA病毒的宿主，但STING在蝙蝠RNA病毒感染过程中的作用尚未阐明。在本研究中，我们鉴定并克隆了巴西无尾蝠（Tadarida brasiliensis）的STING基因，并通过在TB1 Lu细胞中过表达和敲低蝙蝠STING（BatSTING）来测试其诱导IFN-β的能力。此外，我们使用绿色荧光蛋白（GFP）标记的水疱性口炎病毒（VSV）VSV-GFP作为模型来检测BatSTING的抗病毒活性。结果表明，在cGAS刺激下，TB1 Lu细胞中STING的过表达显著抑制了RNA病毒复制，且抗病毒活性与其调节IFN-β和一些干扰素刺激基因（ISGs）基础表达的能力相关。我们还发现，BatSTING在受到多种RNA病毒刺激后能够被激活。对STING缺陷的TB1 Lu细胞的研究结果表明，敲低BatSTING严重阻碍了VSV-GFP触发的IFN-β反应。基于此，我们证实RNA病毒感染期间诱导IFN-β表达需要BatSTING。总之，我们的实验数据清楚地表明，蝙蝠宿主中的STING在介导IFN-β反应和抗RNA病毒感染中发挥着不可替代的作用。
