Single-Cell Profiling of Ebola Virus Disease In Vivo Reveals Viral and Host Dynamics.
Single-Cell Profiling of Ebola Virus Disease In Vivo Reveals Viral and Host Dynamics.
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DOI：
10.1016/j.cell.2020.10.002
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发表时间：
2020-11-25
期刊：
影响因子：
64.5
通讯作者：
Bennett RS
中科院分区：
文献类型：
--
作者：
Kotliar D;Lin AE;Logue J;Hughes TK;Khoury NM;Raju SS;Wadsworth MH 2nd;Chen H;Kurtz JR;Dighero-Kemp B;Bjornson ZB;Mukherjee N;Sellers BA;Tran N;Bauer MR;Adams GC;Adams R;Rinn JL;Melé M;Schaffner SF;Nolan GP;Barnes KG;Hensley LE;McIlwain DR;Shalek AK;Sabeti PC;Bennett RS
埃博拉病毒（EBOV）引起高死亡率的流行病，但由于在高度遏制和爆发环境中进行实验的挑战，该病毒仍未得到充分研究。在这里，我们使用单细胞转录组学和基于 CyTOF 的单细胞蛋白定量来表征恒河猴 EBOV 感染期间的外周免疫细胞。我们获得了 100,000 个转录组和 15,000,000 个蛋白质谱，发现抗原呈递能力降低的未成熟、增殖性单核细胞谱系细胞取代了传统的单核细胞亚群，而淋巴细胞则上调凋亡基因并减少丰度。通过量化细胞内病毒 RNA，我们确定了循环免疫细胞中趋向性的分子决定因素，并检查了病毒和宿主基因表达的时间动态。在受感染的细胞内，EBOV 下调 STAT1 mRNA 和干扰素信号传导，并上调假定的前病毒基因（例如 DYNLL1 和 HSPA5），指定病毒操纵其复制的途径。这项研究揭示了埃博拉病毒的趋向性、复制动力学和引发的免疫反应，并提供了一个在最大程度遏制下表征宿主与病毒相互作用的框架。干扰素反应在受感染细胞中受到抑制，但在旁观者细胞中被激活 EBOV 抑制受感染细胞中的抗病毒基因并上调促病毒基因 增殖性 CD14–CD16– 单核细胞前体在 EVD 期间在循环中扩增 体内循环细胞 EBOV 趋向性表达标记物的鉴定 非人灵长类动物埃博拉病毒 (EBOV) 感染期间循环免疫细胞的单细胞分析可解析病毒的分子相关性向性，表征受感染细胞内的复制动态，并将病毒感染介导的表达变化与细胞因子信号传导引起的表达变化区分开来。
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. Interferon response is suppressed in infected cells but activated in bystander cells EBOV represses antiviral genes and upregulates pro-viral genes in infected cells Proliferative CD14– CD16– monocyte precursors expand in circulation during EVD Identification of expression markers of EBOV tropism for circulating cells in vivo Single-cell profiling of circulating immune cells during Ebola virus (EBOV) infection in non-human primates resolves molecular correlates of viral tropism, characterizes replication dynamics within infected cells, and distinguishes expression changes that are mediated by viral infection from those due to cytokine signaling.
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影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
影响因子：
64.8
作者：
Cote, Marceline;Misasi, John;Ren, Tao;Bruchez, Anna;Lee, Kyungae;Filone, Claire Marie;Hensley, Lisa;Li, Qi;Ory, Daniel;Chandran, Kartik;Cunningham, James
通讯作者：
Cunningham, James
DOI：
10.1126/science.1198704
发表时间：
2011-05-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bendall SC;Simonds EF;Qiu P;Amir el-AD;Krutzik PO;Finck R;Bruggner RV;Melamed R;Trejo A;Ornatsky OI;Balderas RS;Plevritis SK;Sachs K;Pe'er D;Tanner SD;Nolan GP
通讯作者：
Nolan GP
影响因子：
6.4
作者：
Bosio, CM;Aman, MJ;Schmaljohn, A
通讯作者：
Schmaljohn, A
影响因子：
5.4
作者：
Brauburger, Kristina;Boehmann, Yannik;Muehlberger, Elke
通讯作者：
Muehlberger, Elke