Single-Cell Profiling of Ebola Virus Disease In Vivo Reveals Viral and Host Dynamics.
Animals
Antigens, CD
/ metabolism
Biomarkers
/ metabolism
Bystander Effect
Cell Differentiation
Cell Proliferation
Cytokines
/ metabolism
Ebolavirus
/ genetics
Endoplasmic Reticulum Chaperone BiP
Gene Expression Profiling
Gene Expression Regulation
Gene Expression Regulation, Viral
Hemorrhagic Fever, Ebola
/ genetics
Histocompatibility Antigens Class II
/ metabolism
Host-Pathogen Interactions
/ genetics
Interferons
/ genetics
Macaca mulatta
Macrophages
/ metabolism
Monocytes
/ metabolism
Myelopoiesis
RNA, Messenger
/ genetics
Single-Cell Analysis
Time Factors
Transcriptome
/ genetics
CyTOF
Ebola virus
Seq-Well
bystander cells
host-virus interactions
interferon
monocytes
scRNA-Seq
single-cell
viral tropism
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
25 11 2020
25 11 2020
Historique:
received:
12
06
2020
revised:
10
08
2020
accepted:
02
10
2020
pubmed:
8
11
2020
medline:
20
5
2021
entrez:
7
11
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33159858
pii: S0092-8674(20)31308-8
doi: 10.1016/j.cell.2020.10.002
pmc: PMC7707107
pii:
doi:
Substances chimiques
Antigens, CD
0
Biomarkers
0
Cytokines
0
Endoplasmic Reticulum Chaperone BiP
0
HSPA5 protein, human
0
Histocompatibility Antigens Class II
0
RNA, Messenger
0
Interferons
9008-11-1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1383-1401.e19Subventions
Organisme : NIAID NIH HHS
ID : HHSN272200700016I
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI057229
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007753
Pays : United States
Organisme : FIC NIH HHS
ID : K01 TW010853
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI110818
Pays : United States
Organisme : NIAID NIH HHS
ID : U24 AI118672
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201800013C
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests A.K.S. has received compensation for consulting and SAB membership from Honeycomb Biotechnologies, Cellarity, Ochre Bio, Repertoire, and Dahlia Biosciences.
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