乌比奎丁-蛋白质体系统在冠状病毒入侵期间促进了膜融合和脱膜
Xiao Yuan1, Xiaoman Zhang1, Huan Wang1
1Department of Avian Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.
Viruses
|October 28, 2023
概括
在传染性支气管炎病毒 (IBV) 和猪流行性腹病毒 (PEDV) 进入时,无素-蛋白酶体系统 (UPS) 是至关重要的. 抑制UPS阻断病毒膜融合,脱涂和复制,提供潜在的抗病毒标.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 生物化学 生化学
背景情况:
- 无素-蛋白酶体系统 (UPS) 涉及到各种病毒感染.
- 它在传染性支气管炎病毒 (IBV) 和猪流行性腹病毒 (PEDV) 感染中的特定作用仍然在很大程度上不明.
研究的目的:
- 研究UPS在IBV和PEDV生命周期中的作用.
- 为了确定UPS是否对冠状病毒的进入和复制至关重要.
主要方法:
- 使用蛋白酶抑制剂和泛基素激活酶E1抑制剂 (PYR-41) 的UPS的药理抑制.
- 利用R18和DiOC标记的病毒颗粒来追踪病毒进入和膜融合.
- 评估病毒感染性,内化,膜融合,病毒蛋白N降解和初始基因组RNA翻译.
主要成果:
- 抑制UPS严重损害IBV和PEDV感染力和病毒进入.
- 抑制阻止了病毒膜与晚期内体/溶体的融合,而不会影响初始颗粒内部化.
- 蛋白酶体抑制剂阻断了病毒蛋白N的降解,抑制了脱涂和基因组RNA释放,因此抑制了初始翻译.
结论:
- UPS在促进冠状病毒进入方面发挥着关键作用,通过促进病毒颗粒和晚期内分泌体/溶解体之间的膜融合.
- UPS抑制会破坏随后的病毒脱皮,RNA释放和初始翻译,阻碍病毒生命周期.
- 该UPS代表了一个有希望的治疗目标,用于开发针对IBV和PEDV等冠状病毒的新型抗病毒策略.
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