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About:
Ebola Virus VP40 Modulates Cell Cycle and Biogenesis of Extracellular Vesicles
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wasabi.inria.fr
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Academic Article
research paper
schema:ScholarlyArticle
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type
Academic Article
research paper
schema:ScholarlyArticle
isDefinedBy
Covid-on-the-Web dataset
title
Ebola Virus VP40 Modulates Cell Cycle and Biogenesis of Extracellular Vesicles
Creator
Kashanchi, Fatah
Lepene, Benjamin
Cowen, Maria
Erickson, James
Liang, Janie
Prugar, Laura
Zhou, Weidong
Dye, John
Javad, M
Kuhn, Jens
Liotta, Lance
Pleet, Michelle
Stonier, Spencer
Demarino, Catherine
Barclay, Robert
source
PMC
abstract
BACKGROUND: Ebola virus (EBOV) mainly targets myeloid cells; however, extensive death of T cells is often observed in lethal infections. We have previously shown that EBOV VP40 in exosomes causes recipient immune cell death. METHODS: Using VP40-producing clones, we analyzed donor cell cycle, extracellular vesicle (EV) biogenesis, and recipient immune cell death. Transcription of cyclin D1 and nuclear localization of VP40 were examined via kinase and chromatin immunoprecipitation assays. Extracellular vesicle contents were characterized by mass spectrometry, cytokine array, and western blot. Biosafety level-4 facilities were used for wild-type Ebola virus infection studies. RESULTS: VP40 EVs induced apoptosis in recipient T cells and monocytes. VP40 clones were accelerated in growth due to cyclin D1 upregulation, and nuclear VP40 was found bound to the cyclin D1 promoter. Accelerated cell cycling was related to EV biogenesis, resulting in fewer but larger EVs. VP40 EV contents were enriched in ribonucleic acid-binding proteins and cytokines (interleukin-15, transforming growth factor-β1, and interferon-γ). Finally, EBOV-infected cell and animal EVs contained VP40, nucleoprotein, and glycoprotein. CONCLUSIONS: Nuclear VP40 upregulates cyclin D1 levels, resulting in dysregulated cell cycle and EV biogenesis. Packaging of cytokines and EBOV proteins into EVs from infected cells may be responsible for the decimation of immune cells during EBOV pathogenesis.
has issue date
2018-08-30
(
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)
bibo:doi
10.1093/infdis/jiy472
bibo:pmid
30169850
has license
bronze-oa
sha1sum (hex)
44d183ae20a5b4fa9ffa65f25f28134c4ac190d2
schema:url
https://doi.org/10.1093/infdis/jiy472
resource representing a document's title
Ebola Virus VP40 Modulates Cell Cycle and Biogenesis of Extracellular Vesicles
has PubMed Central identifier
PMC6249571
has PubMed identifier
30169850
schema:publication
The Journal of Infectious Diseases
resource representing a document's body
covid:44d183ae20a5b4fa9ffa65f25f28134c4ac190d2#body_text
is
schema:about
of
covid:arg/44d183ae20a5b4fa9ffa65f25f28134c4ac190d2
named entity 'VP40'
named entity 'immune cell'
named entity 'Ebola Virus'
named entity 'Liberia'
named entity 'binding protein'
named entity 'CD8'
named entity 'cell types'
named entity 'Ribociclib'
named entity 'cell cycle'
named entity 'antigen'
named entity 'translocation'
named entity 'Ribociclib'
named entity 'vesicles'
named entity 'transfected'
named entity 'l-glutamine'
named entity 'T-cell'
named entity 'supernatant'
named entity 'exosomal'
named entity 'vesicles'
named entity 'human cytomegalovirus'
named entity 'US Food and Drug Administration'
named entity 'Exosome'
named entity 'immune cells'
named entity 'cell cycle'
named entity '293T cells'
named entity 'Bioinformatic'
named entity 'tetraspanin'
named entity 'Transfected'
named entity 'pathogenesis'
named entity '293T cells'
named entity '293T'
named entity 'T-cell'
named entity 'covalently linked'
named entity 'frame rate'
named entity 'VP40'
named entity 'immune cells'
named entity 'promoter region'
named entity 'transfection'
named entity 'NHP'
named entity 'protein expression'
named entity 'microcentrifuge tubes'
named entity 'virions'
named entity 'cytokine storm'
named entity 'upregulation'
named entity 'granulocyte colony-stimulating factor'
named entity 'RNA genome'
named entity 'cell death'
named entity 'PBMCs'
named entity 'VP40'
named entity 'nonspecific binding'
named entity '293T'
named entity 'Japanese encephalitis'
named entity 'cell morphology'
named entity 'cell type'
named entity 'supernatant'
named entity 'negative sense'
named entity 'VP40'
named entity 'Promega'
named entity 'IGF-1'
named entity 'cyclin D1'
named entity 'host cells'
named entity 'VLP'
named entity 'supernatants'
named entity 'cyclin'
named entity 'VP40'
named entity 'exosomal'
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