Identification of interferon-stimulated genes that attenuate Ebola virus infection.

Animals Blotting, Western Carrier Proteins / genetics Cell Survival / genetics Chlorocebus aethiops Cytoskeletal Proteins Ebolavirus / metabolism Fluorescent Antibody Technique Gene Expression / genetics HEK293 Cells HeLa Cells Humans Immunoprecipitation Interferons / pharmacology Protein Binding Reverse Transcriptase Polymerase Chain Reaction Vero Cells Viral Proteins / metabolism Virus Internalization Virus Replication / genetics

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
11 06 2020
Historique:
received: 23 07 2019
accepted: 17 05 2020
entrez: 13 6 2020
pubmed: 13 6 2020
medline: 25 8 2020
Statut: epublish

Résumé

The West Africa Ebola outbreak was the largest outbreak ever recorded, with over 28,000 reported infections; this devastating epidemic emphasized the need to understand the mechanisms to counteract virus infection. Here, we screen a library of nearly 400 interferon-stimulated genes (ISGs) against a biologically contained Ebola virus and identify several ISGs not previously known to affect Ebola virus infection. Overexpression of the top ten ISGs attenuates virus titers by up to 1000-fold. Mechanistic studies demonstrate that three ISGs interfere with virus entry, six affect viral transcription/replication, and two inhibit virion formation and budding. A comprehensive study of one ISG (CCDC92) that shows anti-Ebola activity in our screen reveals that CCDC92 can inhibit viral transcription and the formation of complete virions via an interaction with the viral protein NP. Our findings provide insights into Ebola virus infection that could be exploited for the development of therapeutics against this virus.

Identifiants

DOI: 10.1038/s41467-020-16768-7 PMID: 32528005 PMC: PMC7289892
pubmed: 32528005
doi: 10.1038/s41467-020-16768-7
pii: 10.1038/s41467-020-16768-7
pmc: PMC7289892
doi:

Substances chimiques

CCDC92 protein, human 0
Carrier Proteins 0
Cytoskeletal Proteins 0
Viral Proteins 0
Interferons 9008-11-1

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

2953

Références

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Auteurs

Makoto Kuroda (M)

Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, WI, 53711, USA.

Peter J Halfmann (PJ)

Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, WI, 53711, USA. peter.halfmann@wisc.edu.
ORCID: 0000-0002-1648-1625

Lindsay Hill-Batorski (L)

Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, WI, 53711, USA.

Makoto Ozawa (M)

Laboratory of Animal Hygiene, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, 890-0065, Japan.
Transboundary Animal Diseases Center, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, 890-0065, Japan.
ORCID: 0000-0002-7731-5321

Tiago J S Lopes (TJS)

Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, WI, 53711, USA.

Gabriele Neumann (G)

Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, WI, 53711, USA.

John W Schoggins (JW)

Department of Microbiology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
ORCID: 0000-0002-7944-6800

Charles M Rice (CM)

Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY, 10065, USA.

Yoshihiro Kawaoka (Y)

Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, WI, 53711, USA. yoshihiro.kawaoka@wisc.edu.
Division of Virology, Department of Microbiology and Immunology, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, 113-8654, Japan. yoshihiro.kawaoka@wisc.edu.
ERATO Infection-Induced Host Responses Project, Japan Science and Technology Agency, Saitama, 332-0012, Japan. yoshihiro.kawaoka@wisc.edu.
ORCID: 0000-0001-5061-8296

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Identification of interferon-stimulated genes...
questionsmedicales.fr › Techniques d'investigation › Techniques de sonde moléculaire › Dosage immunologique › Immunotransfert › Technique de Western › Identification of interferon-stimulated genes...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de transport › Identification of interferon-stimulated genes...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Survie cellulaire › Identification of interferon-stimulated genes...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Cercopithecidae › Cercopithecinae › Cercopithecus › Cercopithecus aethiops › Identification of interferon-stimulated genes...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du cytosquelette › Identification of interferon-stimulated genes...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN de polarité négative › Mononegavirales › Filoviridae › Ebolavirus › Identification of interferon-stimulated genes...
questionsmedicales.fr › Techniques d'investigation › Techniques immunologiques › Technique d'immunofluorescence › Identification of interferon-stimulated genes...
questionsmedicales.fr › Phénomènes génétiques › Expression des gènes › Identification of interferon-stimulated genes...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HEK293 › Identification of interferon-stimulated genes...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HeLa › Identification of interferon-stimulated genes...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Identification of interferon-stimulated genes...
questionsmedicales.fr › Techniques d'investigation › Techniques immunologiques › Immunoprécipitation › Identification of interferon-stimulated genes...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interférons › Identification of interferon-stimulated genes...
questionsmedicales.fr › Métabolisme › Liaison aux protéines › Identification of interferon-stimulated genes...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Techniques d'amplification d'acides nucléiques › Réaction de polymérisation en chaîne › RT-PCR › Identification of interferon-stimulated genes...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules Vero › Identification of interferon-stimulated genes...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines virales › Identification of interferon-stimulated genes...
questionsmedicales.fr › Phénomènes microbiologiques › Phénomènes physiologiques viraux › Pénétration virale › Identification of interferon-stimulated genes...
questionsmedicales.fr › Phénomènes microbiologiques › Phénomènes physiologiques viraux › Réplication virale › Identification of interferon-stimulated genes...