SIRT2通过脱乙G3BP1来负面调节cGAS-STING通路
Yutong Li1, Juntao Bie1, Chen Song1
1Department of Medical Genetics, Center for Medical Genetics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
EMBO reports
|October 23, 2023
概括
赛尔图因2 (SIRT2) 通过去乙化G3BP1.1,在简单疹病毒-1 (HSV-1) 感染期间负面调节cGAS-STING通路. 抑制SIRT2可增强抗病毒免疫力,提供一种潜在的治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 分子生物学分子生物学
背景情况:
- 赛尔图因2 (SIRT2) 参与免疫和炎症.
- 目前尚不清楚SIRT2在DNA病毒感染反应中的作用.
研究的目的:
- 研究SIRT2在调节宿主对简单疹病毒-1 (HSV-1) 感染的反应中的功能.
- 阐明SIRT2调节cGAS-STING信号通路的分子机制.
主要方法:
- 西方涂抹检测蛋白质水平.
- 免疫沉以研究蛋白质相互作用.
- 定量实时PCR测量基因表达.
- 在体内小鼠的HSV-1感染模型.
- 使用选择性SIRT2抑制剂 (AGK2) 的治疗.
主要成果:
- 在HSV-1感染后,SIRT2的表达下调.
- 缺少SIRT2导致I型干扰素 (IFN) 表达的增加.
- SIRT2与G3BP1相互作用并脱乙,抑制cGAS的DNA结合和滴滴形成.
- 使用SIRT2抑制剂AGK2可以保护小鼠免受HSV-1感染,并增强IFN反应.
结论:
- SIRT2通过脱乙G3BP1来负面调节cGAS-STING通路,从而抑制cGAS的激活.
- 调节SIRT2活性是针对HSV-1等病毒感染的潜在治疗策略.
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