Ebola virus infection induces a delayed type I IFN response in bystander cells and the shutdown of key liver genes in human iPSC-derived hepatocytes.
Ebola virus host response
Ebola virus infection
downregulation key liver genes
iPSC-hepatocytes
Journal
Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300
Informations de publication
Date de publication:
11 10 2022
11 10 2022
Historique:
received:
16
02
2022
revised:
08
08
2022
accepted:
09
08
2022
pubmed:
10
9
2022
medline:
15
10
2022
entrez:
9
9
2022
Statut:
ppublish
Résumé
Liver damage and an exacerbated inflammatory response are hallmarks of Ebola virus (EBOV) infection. Little is known about the intrinsic response to infection in human hepatocytes and their contribution to inflammation. Here, we present an induced pluripotent stem cell (iPSC)-derived hepatocyte-like cell (HLC) platform to define the hepato-intrinsic response to EBOV infection. We used this platform to show robust EBOV infection, with characteristic ultrastructural changes and evidence for viral replication. Transcriptomics analysis revealed a delayed response with minimal early transcriptomic changes, followed by a general downregulation of hepatic function and upregulation of interferon signaling, providing a potential mechanism by which hepatocytes participate in disease severity and liver damage. Using RNA-fluorescence in situ hybridization (FISH), we showed that IFNB1 and CXCL10 were mainly expressed in non-infected bystander cells. We did not observe an inflammatory signature during infection. In conclusion, iPSC-HLCs are an immune competent platform to study responses to EBOV infection.
Identifiants
pubmed: 36084636
pii: S2213-6711(22)00412-X
doi: 10.1016/j.stemcr.2022.08.003
pmc: PMC9561183
pii:
doi:
Substances chimiques
RNA
63231-63-0
Interferons
9008-11-1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2286-2302Subventions
Organisme : NIAID NIH HHS
ID : R21 AI135912
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI137793
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007035
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI133486
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NCATS NIH HHS
ID : TL1 TR001410
Pays : United States
Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of interest The authors declare no competing interests.
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