Attenuation of Antiviral Immune Response Caused by Perturbation of TRIM25-Mediated RIG-I Activation under Simulated Microgravity.
Attenuation of Antiviral Immune Response Caused by Perturbation of TRIM25-Mediated RIG-I Activation under Simulated Microgravity.
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DOI：
10.1016/j.celrep.2020.108600
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发表时间：
2021-01
期刊：
影响因子：
8.8
通讯作者：
Lv-yun Zhu;Li Nie;Si-si Xie;Ming Li;Chushu Zhu;Xinyuan Qiu;Jingyu Kuang;Chuanyang Liu;
中科院分区：
文献类型：
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作者：
Lv-yun Zhu;Li Nie;Si-si Xie;Ming Li;Chushu Zhu;Xinyuan Qiu;Jingyu Kuang;Chuanyang Liu;
微重力是空间飞行的一个主要环境因素，它会引发免疫系统失调，增加深空探索机组人员的临床风险。然而，在动物模型中，微重力对免疫系统不利影响的系统研究和分子机制有限。为开展空间免疫学研究，建立了微重力条件下斑马鱼疾病的地面模型。RNA测序分析表明，维甲酸诱导基因（RIG）-I样受体（RLR）和Toll样受体（TLR）信号通路受到模拟微重力（Sμg）的显著损害。TRIM 25是RLR信号传导的必需E3，在Sμg下被抑制，阻碍了RIG-I的K63连接的泛素化和随后的抗病毒免疫应答的功能诱导正反馈回路。这些机制为更好地理解微重力对宿主抗病毒免疫的影响和原理提供了见解，并为制定可在空间飞行期间预防和控制病毒性疾病的战略提供了广泛的潜在影响。
Microgravity is a major environmental factor of space flight that triggers dysregulation of the immune system and increases clinical risks for deep-space-exploration crews. However, systematic studies and molecular mechanisms of the adverse effects of microgravity on the immune system in animal models are limited. Here, we establish a ground-based zebrafish disease model of microgravity for the research of space immunology. RNA sequencing analysis demonstrates that the retinoic-acid-inducible gene (RIG)-I-like receptor (RLR) and the Toll-like receptor (TLR) signaling pathways are significantly compromised by simulated microgravity (Sμg). TRIM25, an essential E3 for RLR signaling, is inhibited under Sμg, hampering the K63-linked ubiquitination of RIG-I and the following function-induction positive feedback loop of antiviral immune response. These mechanisms provide insights into better understanding of the effects and principles of microgravity on host antiviral immunity and present broad potential implications for developing strategies that can prevent and control viral diseases during space flight.