在多个家族的病毒的芽和复制中,ALIX的CCL2-介导调节的影响
Dina Mofed1, Anjali Gowripalan1, Jacob Berrigan1
1Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.
mBio
|September 25, 2025
概括
C-C 动机连接体2 (CCL2) 信号调动ALG-2交互蛋白X (ALIX) 进行HIV-1释放. 阻止CCL2阻止ALIX的调动,抑制病毒的产生,但CCL2的添加恢复释放. 这种机制会影响多个病毒家族.
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:
- 通过影响ALG-2相互作用蛋白X (ALIX) 的局部化,CCL2信号调节HIV-1的芽和释放.
- CCL2信号调动ALIX从F-actin细胞骨到细胞质,使其可用于病毒组装.
- 之前的研究方法涉及CCL2免疫减弱,导致ALIX封存和抑制病毒产生.
研究的目的:
- 开发一种新的工具,通过基因阻断CCL2信号来研究HIV的芽和释放.
- 研究CCL2信号和ALIX动员在各种病毒复制中的作用.
- 确认HIV-1释放与ALIX在细胞质中的可用性之间的依赖.
主要方法:
- 开发出了CRISPR-Cas9淘汰 (KO) HeLa细胞系,用于CCL2和/或CCR2.
- 在KO和对照细胞中评估ALIX局部化 (细胞质与F-actin结合).
- 量化KO细胞中的病毒产生,有或没有CCL2添加,测试多种病毒 (HIV-1,SIV,EIAV,HSV-1,DENV,HAZV).
主要成果:
- CCL2或CCR2淘汰细胞显示ALIX被隔离到F-actin,并减少了HIV-1生产的10倍.
- 将CCL2添加到CCL2KO细胞中,恢复了ALIX到细胞质中,并挽救了HIV-1释放到高于对照水平.
- Simian Immunodeficiency Virus (SIV) 和 Equine Infectious Anemia Virus (EIAV) 的芽/释放被抑制在CCL2KO细胞中,并被CCL2拯救; 疹简单病毒1型 (HSV-1) 和登革热病毒 (DENV) 复制没有受到影响; Hazara病毒 (HAZV) 复制受到了影响.
结论:
- CCL2信号和ALIX动员对于HIV-1,SIV和EIAV的释放至关重要.
- 开发的CRISPR-Cas9 KO系统提供了一个新的工具来研究病毒释放机制,而无需对病毒组件或ESCRT机械进行遗传操纵.
- 通过CCL2介导的ALIX动员在多个家族的病毒的复制策略中发挥作用.
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