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单细胞分析体内埃博拉病毒揭示病毒和宿主的动态调控
作者:小柯机器人 发布时间:2020/11/9 22:04:44

哈佛医学院Dylan Kotliar和哈佛大学Aaron E. Lin研究团队合作,通过体内埃博拉病毒(EBOV)的单细胞分析揭示了病毒和宿主动态变化。2020年11月6日,《细胞》杂志在线发表了这项成果。

研究人员使用单细胞转录组学和基于CyTOF的单细胞蛋白质定量来表征恒河猴EBOV感染时外周免疫细胞的变化。研究人员获得了100000个转录组和15000000个蛋白质谱,并发现低抗原呈递能力的未成熟、增殖单核细胞取代了正常单核细胞亚群,而淋巴细胞的凋亡基因上调并且细胞数量减少。

通过量化细胞内病毒RNA,研究确定了循环免疫细胞间趋向性的分子决定因素,并研究了病毒和宿主基因表达的时间动态。在受感染的细胞中,EBOV下调STAT1的mRNA和干扰素信号传导,并上调可能的前病毒基因(例如DYNLL1和HSPA5),从而开启病毒操纵的复制途径。

这项研究揭示了EBOV的趋向性、复制动力学和引发的免疫反应,并为表征宿主-病毒在最大遏制条件下的相互作用提供了框架。

据了解,埃博拉病毒是引起高死亡率的流行病,但由于在高污染和暴发环境中进行实验存在困难,目前其仍未被充分研究。

附:英文原文

Title: Single-Cell Profiling of Ebola Virus Disease In Vivo Reveals Viral and Host Dynamics

Author: Dylan Kotliar, Aaron E. Lin, James Logue, Travis K. Hughes, Nadine M. Khoury, Siddharth S. Raju, Marc H. Wadsworth, Han Chen, Jonathan R. Kurtz, Bonnie Dighero-Kemp, Zach B. Bjornson, Nilanjan Mukherjee, Brian A. Sellers, Nancy Tran, Matthew R. Bauer, Gordon C. Adams, Ricky Adams, John L. Rinn, Marta Melé, Stephen F. Schaffner, Garry P. Nolan, Kayla G. Barnes, Lisa E. Hensley, David R. McIlwain, Alex K. Shalek, Pardis C. Sabeti, Richard S. Bennett

Issue&Volume: 2020-11-06

Abstract: Ebola virus (EBOV) causes epidemics with high mortality yet remains understudied due to the challenge of experimentation in high-containment and outbreak settings. Here, we used single-cell transcriptomics and CyTOF-based single-cell protein quantification to characterize peripheral immune cells during EBOV infection in rhesus monkeys. We obtained 100,000 transcriptomes and 15,000,000 protein profiles, finding that immature, proliferative monocyte-lineage cells with reduced antigen-presentation capacity replace conventional monocyte subsets, while lymphocytes upregulate apoptosis genes and decline in abundance. By quantifying intracellular viral RNA, we identify molecular determinants of tropism among circulating immune cells and examine temporal dynamics in viral and host gene expression. Within infected cells, EBOV downregulates STAT1 mRNA and interferon signaling, and it upregulates putative pro-viral genes (e.g., DYNLL1 and HSPA5), nominating pathways the virus manipulates for its replication. This study sheds light on EBOV tropism, replication dynamics, and elicited immune response and provides a framework for characterizing host-virus interactions under maximum containment.

DOI: 10.1016/j.cell.2020.10.002

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31308-8

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/