CircCBP通过干扰vRNP活动和增强抗病毒免疫反应来抑制流感A病毒复制
Xinli Yao1,2, Mingge Wang1,3, Xiaomei Tong1,2
1CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Journal of medical virology
|June 12, 2025
概括
循环CREB结合蛋白 (circCBP) 通过破坏病毒活性和增强抗病毒免疫反应来抑制流感A病毒 (IAV) 复制. 这种循环RNA为新型抗病毒疗法提供了潜在的目标.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 甲型流感病毒 (IAV) 导致季节性和流行性流感.
- 宿主非编码RNA,包括循环RNA (circRNA),都与IAV复制有关.
- 在IAV复制中circRNAs的确切作用仍然在很大程度上是未知的.
研究的目的:
- 为了研究circRNAs在IAV复制中的功能.
- 为了确定规范IAV复制和宿主抗病毒反应的特定circRNAs.
- 阐明circRNAs调节IAV感染的分子机制.
主要方法:
- 在IAV感染的A549细胞中分析circRNAs的RNA深度测序.
- 过度表达和敲击实验,以评估circCBP对IAV复制的影响.
- 共同免疫沉和西部斑点分析蛋白质-RNA相互作用.
- 评估病毒复制,vRNP活性和干扰素-β (IFN-β) 生产.
主要成果:
- 循环CREB结合蛋白 (circCBP) 表达在IAV感染和干扰素治疗时被上调.
- circCBP的过度表达抑制了IAV的复制,而它的倒退促进了它.
- circCBP与病毒核蛋白 (NP) 相互作用,阻碍其与聚合酶子单元 (PB1,PB2) 的相互作用,并阻断vRNP活性.
- circCBP与非结构蛋白1 (NS1) 结合,减轻其抑制抗病毒免疫力的作用.
- circCBP通过增强G3BP1的寡合化来促进压力颗粒的形成,从而导致IFN-β转录的增加.
结论:
- circCBP作为一种针对IAV的新型抗病毒因子.
- circCBP通过多种机制抑制IAV复制,包括直接干扰病毒成分和增强宿主抗病毒免疫力.
- circCBP在压力颗粒形成和IFN-β产生中的作用强调了它在先天免疫反应中的重要性.
- circRNAs,特别是circCBP,代表了开发抗流感新抗病毒策略的有希望的途径.
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