转化应激反应的差调节由疹病毒的ubiquitin deconjugases
Jiangnan Liu1, Noemi Nagy1, Carlos Mario Ayala-Torres1
1Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
The FEBS journal
|October 12, 2025
概括
来自EBV,HCMV和KSHV的病毒性泛素脱酶 (vDUB) 通过防止蛋白质泛素化和拯救基质来抵消核糖体质量控制 (RQC). HSV1 vDUB显示部分有效性,突出了病毒在调节转化压力的策略.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 细胞应激反应的应激反应
背景情况:
- 病毒规避宿主抗病毒机制的策略,特别是核糖体质量控制 (RQC),仍然在很大程度上是未知的.
- RQC控制蛋白质翻译忠实性,核糖体循环和应激反应,这些对细胞防御至关重要.
- 人类致病性疹病毒在体膜蛋白内编码病毒解结酶 (vDUB),可能调节宿主反应.
研究的目的:
- 调查疹病毒编码的vDUBs在转化应激期间抵消RQC激活中的作用.
- 为了确定vDUB是否可以干扰核糖体蛋白质的泛化和UFMylation,关键的RQC触发器.
- 评估VDUB对RQC基质降解,mRNA读透和ER相关RQC的影响.
主要方法:
- 利用基于细胞的测定与翻译抑制剂 (亚尼索米辛) 诱导翻译压力.
- 研究了核糖体蛋白质 (RPS10,RPS20,RPS3) 的无化状态和RPL26.6的UFMylation.
- 监测了RQC和ER-RQC基质的降解,mRNA读透,ER-phagy和综合应激反应 (ISR) 的激活.
主要成果:
- 来自埃普斯坦-巴尔病毒 (EBV),人类细胞巨核病毒 (HCMV) 和卡波西肉瘤病毒 (KSHV) 的vDUBs有效抑制了RPS无化和RPL26 UFMylation.
- 这些vDUBs从降解中拯救了RQC基质,促进了停滞的mRNA的阅读,并抑制了ER-phagy.
- 简单疹病毒-1 (HSV1) vDUB 抑制了 RPS 无化和拯救了 RQC 基质,但未能抵消 RPL26 UFMylation,ER-phagy 或 ISR 激活.
结论:
- 疹病毒vDUB在颠覆RQC途径方面表现出明显的能力,EBV,HCMV和KSHVvDUB表现出比HSV1vDUB更广泛的干扰.
- 这些发现揭示了微妙的病毒策略来操纵翻译应激反应以促进复制.
- 了解这些病毒对策,可以了解宿主-病原体相互作用和潜在的抗病毒点.
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