通过综合应激反应途径激活ATF3,调节先天免疫反应以限制寨卡病毒的传播
Pheonah Badu1,2, Gabriele Baniulyte1,2, Morgan A Sammons1,2
1Department of Biological Sciences, College of Arts and Sciences, University at Albany-SUNY, Albany, New York, USA.
Journal of virology
|August 30, 2024
概括
寨卡病毒感染激活了综合应激反应,诱导激活转录因子3 (ATF3). 然后ATF3限制病毒复制并增强抗病毒基因表达,揭示了一个关键的宿主防御机制.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 寨卡病毒 (ZIKV) 感染通过改变宿主细胞功能,导致严重的健康问题.
- 由ZIKV诱导的转录变化和宿主抗病毒反应的机制尚未完全理解.
- 在ZIKV感染期间,激活转录因子3 (ATF3) 的高调,但其激活途径和作用尚不清楚.
研究的目的:
- 为了定义ZIKV感染期间ATF3激活的途径.
- 阐明ATF3在ZIKV复制和宿主防御中的作用.
- 研究ZIKV诱导的应激反应与先天免疫之间的相互作用.
主要方法:
- 利用抑制剂和RNA干扰方法来研究ATF3激活.
- 使用CRISPR-Cas9基因编辑来删除ATF3.
- 分析了抗病毒基因的表达,包括STAT1,作为对ATF3.3的反应.
主要成果:
- 齐克病毒感染激活了综合应激反应途径,导致ATF4介导的ATF3.3诱导.
- 由于ATF3缺乏,ZIKV基因表达增加.
- ATF3增强了抗病毒基因的表达,并促进了ATF3依赖的抗ZIKV反应.
结论:
- 齐克病毒感染触发了综合应激反应,激活了ATF3.
- 通过调节抗病毒基因,ATF3在限制ZIKV复制方面发挥着关键作用.
- 这项研究揭示了细胞应激途径与对ZIKV. 病毒的先天性免疫反应之间的联系.
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