一个dsRNA病毒转录调节器通过劫持宿主同转录因子DHX9来逃避天生的免疫力
Xueyang Pang1, Shiyu Liu1, Yixiao Zhu2
1Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|December 23, 2025
概括
哺乳动物的ortoreovirus外囊蛋白 σ3 作为病毒转录调节器,通过抑制DHX9螺旋酶和破坏RNA聚合酶II招募来抑制宿主抗病毒基因表达.
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:
- 病毒转录调节器 (vTRs) 在病毒感染期间调节宿主基因表达.
- 了解vTR机制对于开发抗病毒疗法至关重要.
- 哺乳动物体内病毒 (REOV) 作为研究宿主天生的免疫的病毒对抗性的模型.
研究的目的:
- 确定新型病毒机制来对抗宿主天生的免疫反应.
- 为了阐明REOV的外体蛋白 σ3 如何作为vTR.
- 为了研究 σ3,宿主因子和基因转录之间的分子相互作用.
主要方法:
- 利用REOV作为研究病毒与宿主相互作用的模型系统.
- 研究了REOV外蛋白 σ3与宿主酶 DHX9.9之间的相互作用.
- 分析了σ3对NF-κB基因表达和RNA聚合酶II (Pol II) 招募的影响.
- 检查了R循环形成和Pol II暂停释放动态.
主要成果:
- 确定了REOV外囊蛋白σ3作为一种抑制NF-κB基因表达的vTR.
- 证明 σ3 与宿主酶 DHX9.9 直接相互作用.
- 证明 σ3 破坏了 DHX9 和 Pol II 之间的相互作用,损害了 Pol II 招募.
- 发现s3抑制DHX9酶活性,导致R循环积累和抑制NF-κB表达.
结论:
- REOV σ3蛋白采用了前所未有的策略来抑制宿主抗病毒基因表达.
- 病毒对抗性包括对宿主转录因子DHX9.9的直接调节.
- 由 σ3 干扰 DHX9 功能,抑制了NF-κB 转录启动和延长的关键步骤.
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