通过腺病毒突变体激活不同的dsRNA传感器,通过RNP颗粒的差异组合
bioRxiv : the preprint server for biology
|February 27, 2026
概括
腺病毒感染劫持了细胞应激反应. 它差异地激活抗病毒途径并形成独特的RNP颗粒,影响病毒复制和宿主防御.
科学领域:
- 分子生物学分子生物学
- 病毒学 病毒学
- 细胞生物学 细胞生物学
背景情况:
- 双链RNA (dsRNA) 识别激活抗病毒防御,包括PKR和OAS3/RNase L通路.
- 这种激活导致转化停止和RNA衰变,伴随着压力颗粒 (SG) 和RNase L-依赖体 (RLB) 的形成.
- adenovirus 感染对这些 dsRNA 传感器和 RNP 颗粒组件的影响尚未完全理解.
研究的目的:
- 研究腺病毒感染如何差异调节dSRNA传感器和RNP颗粒组装.
- 阐明病毒组件的不同作用,如拼接缺陷突变体和病毒相关 (VA) RNAs,在触发细胞反应.
- 了解将dSRNA传感与转化控制和病毒感染期间的RNP凝结物形成联系在一起的机制.
主要方法:
- 感染特定突变的腺病毒 (拼接缺陷的 ΔE4 和 VA RNA 缺陷突变).
- 对dsRNA积累,PKR和OAS3/RNase L激活的分析.
- 应力颗粒 (SG) 和RNase L-依赖体 (RLB) 的蛋白质组分析.
- 评估PKR和RNase L对颗粒形成的依赖性.
- 研究翻译性逮捕机制,包括eIF2α酸化.
主要成果:
- 拼接缺陷的 ΔE4 突变导致 dsRNA 积累,激活 PKR 和 OAS3 / RNase L,促进类似 RLB 的颗粒形成.
- 缺乏病毒关联 (VA) RNA 的突变体会触发PKR激活和SG组合,尽管没有可检测的dsRNA.
- 蛋白质组分析揭示了正规的SG和RLB中不同的蛋白质组成,反映在病毒诱导的颗粒中.
- 由ΔVA诱导的颗粒是PKR依赖的,而由ΔE4诱导的RLB型颗粒则独立于PKR和RNase L.形成.
- 在 ΔE4 感染细胞中的颗粒组合与独立于 eIF2α 酸化的转化停止相吻合.
结论:
- 腺病毒感染差异调节dSRNA传感途径和RNP颗粒组合.
- 不同的病毒突变通过不同的机制诱导特定类型的RNP颗粒 (SG或RLB类).
- 在病毒感染期间,有新的途径将核dsRNA传感与转化控制和RNP颗粒组装联系起来,独立于eIF2α酸化.
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