Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Cell, 2020-11, Vol.183 (5), p.1383-1401.e19

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •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.