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Cell DOI:10.1016/j.cell.2020.10.002

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

Publication TypeJournal Article
Year of Publication2020
AuthorsKotliar, D, Lin, AE, Logue, J, Hughes, TK, Khoury, NM, Raju, SS, Wadsworth, MH, 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
JournalCell
Volume183
Issue5
Pages1383-1401.e19
Date Published2020 Nov 25
ISSN1097-4172
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.

DOI10.1016/j.cell.2020.10.002
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/33159858?dopt=Abstract

Alternate JournalCell
PubMed ID33159858
PubMed Central IDPMC7707107
Grant ListHHSN272200700016I / AI / NIAID NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
K01 TW010853 / TW / FIC NIH HHS / United States
U19 AI110818 / AI / NIAID NIH HHS / United States
U24 AI118672 / AI / NIAID NIH HHS / United States
HHSN272201800013C / AI / NIAID NIH HHS / United States