在疹病毒感染期间追踪STING外细胞形成途径
Christos Dogrammatzis1, Rabina Saud1, Hope Waisner1
1Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USA.
mBio
|March 12, 2024
概括
在HSV-1感染期间,干扰素基因刺激器 (STING) 通过CD63-依赖途径被包装成细胞外囊泡 (EVs). 这种病毒诱导的STING外细胞形成了感染的微环境,并且在疹病毒菌株之间存在差异.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 细胞生物学 细胞生物学
背景情况:
- 干扰素基因刺激器 (STING) 是先天免疫系统的关键组成部分,能够感知病原体DNA并启动抗病毒反应,包括I型干扰素的产生.
- 疹简单病毒1型 (HSV-1) 已经进化了逃避STING介导免疫力的机制.
- 此前,STING被发现包装在HSV-1感染细胞的细胞外囊泡 (EV) 中,然后为受体细胞提供抗病毒保护.
研究的目的:
- 为了阐明在HSV-1感染期间STING的细胞外移路径.
- 为了确定宿主因素和病毒触发器,涉及到STING外细胞.
- 调查STING外细胞分裂是否是不同疹病毒中保存的机制.
主要方法:
- 利用 CD63 淘汰细胞来评估 STING 异位细胞形成的途径.
- 雇员共同定位研究和共同分离试验分析STING和CD63的关联.
- 研究了Golgi贩运,STING棕化,STIM1结合和使用药理抑制剂和基因操纵的病毒复制的作用.
- 在不同的疹病毒感染 (HSV-1,HSV-2,VZV,HCMV) 中比较了STING外细胞和EV抗病毒活性.
主要成果:
- STING外细胞分裂依赖于CD63通路,与CD63在细胞质结构和外分数中同定位.
- 通过戈尔吉器官的STING贩运,STING棕化和STIM1对ER的绑定对于STING外细胞形成至关重要.
- HSV-1复制和晚期基因表达触发了 CD63 异位细胞分裂,这对于 STING 异位细胞分裂是必需的;然而,HSV-2 (((G)) 与 VZV 和 HCMV 不同,没有诱导 CD63 或 STING 异位细胞分裂.
结论:
- 刺痛细胞外是一种病毒诱导的过程,特别是由HSV-1,VZV和HCMV引发,但不是HSV-2 (G),突出显示病毒特异性免疫调节机制.
- 该途径涉及CD63介导的外细胞形成,Golgi贩运和STING后翻译性修饰,表明复杂的宿主-病原体相互作用.
- 来自HSV-1和HSV-2感染细胞的EV的差异性外细胞和抗病毒能力表明,这些病毒采用不同的策略来塑造感染微环境.
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