Identification of interferon-stimulated genes that attenuate Ebola virus infection

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...

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Published inNature communications Vol. 11; no. 1; pp. 2953 - 14
Main Authors Kuroda, Makoto, Halfmann, Peter J., Hill-Batorski, Lindsay, Ozawa, Makoto, Lopes, Tiago J. S., Neumann, Gabriele, Schoggins, John W., Rice, Charles M., Kawaoka, Yoshihiro
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 11.06.2020
Nature Publishing Group
Nature Portfolio
Subjects
49/40
631/250/127/1212
631/326/596/2042
631/326/596/2556
631/326/596/2557
Animals
Blotting, Western
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cell Survival - genetics
Cell Survival - physiology
Chlorocebus aethiops
Cytoskeletal Proteins
Drug development
Ebola virus
Ebolavirus
Ebolavirus - metabolism
Ebolavirus - pathogenicity
Fluorescent Antibody Technique
Gene Expression - genetics
Genes
HEK293 Cells
HeLa Cells
Humanities and Social Sciences
Humans
Immunoprecipitation
Infections
Interferon
Interferons - pharmacology
Libraries
multidisciplinary
Outbreaks
Protein Binding
Replication
Reverse Transcriptase Polymerase Chain Reaction
Science
Science (multidisciplinary)
Transcription
Vero Cells
Viral diseases
Viral Proteins - metabolism
Virions
Virus Internalization
Virus Replication - genetics
Virus Replication - physiology
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Abstract 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. Here, Kuroda et al. screen a library of nearly 400 interferon-stimulated genes (ISGs) and identify several ISGs that inhibit Ebola virus entry, viral transcription/replication, or virion formation. The study provides insights into interactions between Ebola and the host cells.
AbstractList 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.Here, Kuroda et al. screen a library of nearly 400 interferon-stimulated genes (ISGs) and identify several ISGs that inhibit Ebola virus entry, viral transcription/replication, or virion formation. The study provides insights into interactions between Ebola and the host cells.
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.
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. Here, Kuroda et al. screen a library of nearly 400 interferon-stimulated genes (ISGs) and identify several ISGs that inhibit Ebola virus entry, viral transcription/replication, or virion formation. The study provides insights into interactions between Ebola and the host cells.
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.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.
Here, Kuroda et al. screen a library of nearly 400 interferon-stimulated genes (ISGs) and identify several ISGs that inhibit Ebola virus entry, viral transcription/replication, or virion formation. The study provides insights into interactions between Ebola and the host cells.
ArticleNumber 2953
Author Schoggins, John W.
Rice, Charles M.
Kuroda, Makoto
Kawaoka, Yoshihiro
Neumann, Gabriele
Lopes, Tiago J. S.
Hill-Batorski, Lindsay
Halfmann, Peter J.
Ozawa, Makoto
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Snippet The West Africa Ebola outbreak was the largest outbreak ever recorded, with over 28,000 reported infections; this devastating epidemic emphasized the need to...
Here, Kuroda et al. screen a library of nearly 400 interferon-stimulated genes (ISGs) and identify several ISGs that inhibit Ebola virus entry, viral...
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SubjectTerms 49/40
631/250/127/1212
631/326/596/2042
631/326/596/2556
631/326/596/2557
Animals
Blotting, Western
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cell Survival - genetics
Cell Survival - physiology
Chlorocebus aethiops
Cytoskeletal Proteins
Drug development
Ebola virus
Ebolavirus
Ebolavirus - metabolism
Ebolavirus - pathogenicity
Fluorescent Antibody Technique
Gene Expression - genetics
Genes
HEK293 Cells
HeLa Cells
Humanities and Social Sciences
Humans
Immunoprecipitation
Infections
Interferon
Interferons - pharmacology
Libraries
multidisciplinary
Outbreaks
Protein Binding
Replication
Reverse Transcriptase Polymerase Chain Reaction
Science
Science (multidisciplinary)
Transcription
Vero Cells
Viral diseases
Viral Proteins - metabolism
Virions
Virus Internalization
Virus Replication - genetics
Virus Replication - physiology
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Title Identification of interferon-stimulated genes that attenuate Ebola virus infection
URI https://link.springer.com/article/10.1038/s41467-020-16768-7
https://www.ncbi.nlm.nih.gov/pubmed/32528005
https://www.proquest.com/docview/2412192667
https://www.proquest.com/docview/2412994752
https://pubmed.ncbi.nlm.nih.gov/PMC7289892
https://doaj.org/article/15a4bdc76f7d489a88f817318de56695
Volume 11
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