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在活体中对埃博拉病毒病单细胞分析揭示了病毒和宿主动态

Dylan Kotliar¹, Aaron E Lin², James Logue³

¹Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.

|November 7, 2020

概括

埃博拉病毒感染会改变免疫细胞,以不成熟的形式取代单细胞,并减少淋巴细胞. 病毒操纵宿主基因,影响干扰素信号传递并促进自身复制.

科学领域:

免疫学
病毒学
分子生物学

背景情况:

埃博拉病毒 (EBOV) 导致高死亡率的流行病,但难以研究.
了解宿主病毒相互作用对于开发有效的对策至关重要.

研究的目的:

在 rhesus 子中描述 EBOV 感染期间的外周免疫细胞反应.
确定EBOV热带和复制的分子机制.

主要方法:

使用单细胞转录组学和单细胞蛋白质量测量.
分析了超过10万个转录组和1500万个蛋白质样本.
研究了细胞内病毒RNA量化和宿主基因表达动态.

主要成果:

EBOV感染导致常规单细胞被不成熟,功能较差的单细胞系细胞所取代.
淋巴细胞呈现出增加的细胞亡和减少的丰度.
EBOV降低了STAT1mRNA和干扰素信号传递,同时在受感染细胞内增加了DYNLL1和HSPA5等亲病毒基因.

结论:

这项研究透露了通过操纵宿主细胞通路对EBOV热带性和复制策略的关键见解.
这些发现为了解高封闭环境中的宿主病毒相互作用提供了全面的框架.
描述的免疫细胞动态和病毒操纵途径为治疗干预提供了潜在的目标.

关键词:

美国埃博拉病毒这样就好了旁观者细胞主体病毒的相互作用干扰素单细胞 scRNA-Seq 在一个细胞病毒热带性

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