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与维相关的US28迅速调节Akt活性,以抑制单细胞中的HCMV溶性复制
bioRxiv : the preprint server for biology
|September 21, 2023
概括
人类细胞巨型病毒 (HCMV) 使用病毒US28蛋白来在单细胞中建立无声感染. 维里昂产生的US28调节了Akt酸化,使HCMV进入静止状态.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 人类细胞巨乳病毒 (HCMV) 在单细胞中建立静止感染,这对其传播至关重要.
- 尚不完全了解HCMV在单细胞中确立这些无声感染的确切机制.
- 已知病毒G蛋白结合受体US28对于髓状细胞的静态感染至关重要.
研究的目的:
- 阐明病毒G蛋白结合受体US28在确定单细胞中HCMV静止感染中的作用.
- 为了研究US28促进HCMV延迟的机制.
- 为了确定US28对宿主细胞信号通路在HCMV感染期间的影响.
主要方法:
- 使用了缺乏US28 (US28Δ) 的重组突变HCMV来研究其功能.
- 在受感染的单细胞中追踪US28的输送和合成.
- 在感染野生型 (WT) 和US28Δ HCMV的单细胞中分析了Akt酸化模式.
- 研究了调节Akt酸化对病毒复制的影响.
主要成果:
- 与维相关的US28迅速传递给单细胞,而新合成的US28则延迟.
- 缺少US28 (US28Δ) 的HCMV无法建立静止感染,并经历生产性的毒性复制.
- US28Δ感染导致Akt在Ser473和Thr308的双酸化,与WT感染不同,该感染显示了特定位点的酸化.
- 抑制阿克特双酸化阻止US28Δ的溶性复制,而构成性阿克特酸化触发了WT感染中的溶性复制.
结论:
- 由Virion提供的US28在调节Akt活动中起着至关重要的作用.
- 这种US28的调制对于HCMV在初级感染后在单细胞中建立静止感染至关重要.
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