MersV1, Main, Curation, bibRecord, 001671

Middle East respiratory syndrome coronavirus ORF4b protein inhibits type I interferon production through both cytoplasmic and nuclear targets

Identifieur interne : 001671 ( Main/Curation ); précédent : 001670; suivant : 001672

Middle East respiratory syndrome coronavirus ORF4b protein inhibits type I interferon production through both cytoplasmic and nuclear targets

Auteurs : Yang Yang [République populaire de Chine] ; Fei Ye [République populaire de Chine] ; Na Zhu [République populaire de Chine] ; Wenling Wang [République populaire de Chine] ; Yao Deng [République populaire de Chine] ; Zhengdong Zhao [République populaire de Chine] ; Wenjie Tan [République populaire de Chine]

Source :

Scientific Reports [ 2045-2322 ] ; 2015.

RBID : PMC:4668369

Descripteurs français

English descriptors

KwdEn :
- Adaptor Proteins, Signal Transducing (metabolism), Cell Nucleus (metabolism), Cell Nucleus (virology), Cytoplasm (metabolism), Cytoplasm (virology), DEAD Box Protein 58 (genetics), DEAD Box Protein 58 (metabolism), HeLa Cells (virology), Host-Pathogen Interactions, Humans, I-kappa B Kinase (metabolism), Interferon Regulatory Factor-3 (genetics), Interferon Regulatory Factor-3 (metabolism), Interferon Regulatory Factor-7 (metabolism), Interferon-Induced Helicase, IFIH1 (genetics), Interferon-Induced Helicase, IFIH1 (metabolism), Interferon-beta (genetics), Interferon-beta (metabolism), Middle East Respiratory Syndrome Coronavirus (pathogenicity), Phosphorylation, Protein-Serine-Threonine Kinases (metabolism), Viral Proteins (genetics), Viral Proteins (metabolism), Viral Proteins (pharmacology).
MESH :
- chemical , genetics : DEAD Box Protein 58, Interferon Regulatory Factor-3, Interferon-Induced Helicase, IFIH1, Interferon-beta, Viral Proteins.
- chemical , metabolism : Adaptor Proteins, Signal Transducing, DEAD Box Protein 58, I-kappa B Kinase, Interferon Regulatory Factor-3, Interferon Regulatory Factor-7, Interferon-Induced Helicase, IFIH1, Interferon-beta, Protein-Serine-Threonine Kinases, Viral Proteins.
- metabolism : Cell Nucleus, Cytoplasm.
- pathogenicity : Middle East Respiratory Syndrome Coronavirus.
- chemical , pharmacology : Viral Proteins.
- virology : Cell Nucleus, Cytoplasm, HeLa Cells.
- Host-Pathogen Interactions, Humans, Phosphorylation.

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel and highly pathogenic human coronavirus and has quickly spread to other countries in the Middle East, Europe, North Africa and Asia since 2012. Previous studies have shown that MERS-CoV ORF4b antagonizes the early antiviral alpha/beta interferon (IFN-α/β) response, which may significantly contribute to MERS-CoV pathogenesis; however, the underlying mechanism is poorly understood. Here, we found that ORF4b in the cytoplasm could specifically bind to TANK binding kinase 1 (TBK1) and IκB kinase epsilon (IKKε), suppress the molecular interaction between mitochondrial antiviral signaling protein (MAVS) and IKKε and inhibit IFN regulatory factor 3 (IRF3) phosphorylation and subsequent IFN-β production. Further analysis showed that ORF4b could also inhibit IRF3 and IRF7-induced production of IFN-β, whereas deletion of the nuclear localization signal of ORF4b abrogated its ability to inhibit IRF3 and IRF7-induced production of IFN-β, but not IFN-β production induced by RIG-I, MDA5, MAVS, IKKε and TBK-1, suggesting that ORF4b could inhibit the induction of IFN-β in both the cytoplasm and nucleus. Collectively, these results indicate that MERS-CoV ORF4b inhibits the induction of type I IFN through a direct interaction with IKKε/TBK1 in the cytoplasm and also in the nucleus with unknown mechanism. Viruses have evolved multiple strategies to evade or thwart a host’s antiviral responses. A novel human coronavirus (HCoV), Middle East respiratory syndrome coronavirus (MERS-CoV), is distinguished from other coronaviruses by its high pathogenicity and mortality. However, virulence determinants that distinguish MERS-CoV from other HCoVs have yet to be identified. MERS-CoV ORF4b antagonizes the early antiviral response, which may contribute to MERS-CoV pathogenesis. Here, we report the identification of the interferon (IFN) antagonism mechanism of MERS-CoV ORF4b. MERS-CoV ORF4b inhibits the production of type I IFN through a direct interaction with IKKε/TBK1 in the cytoplasm and also in the nucleus with unknown mechanism. These findings provide a rationale for the novel pathogenesis of MERS-CoV as well as a basis for developing a candidate therapeutic against this virus.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4668369

DOI: 10.1038/srep17554
PubMed: 26631542
PubMed Central: 4668369

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PMC:4668369

Le document en format XML

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Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Scientific Reports</title>
<idno type="eISSN">2045-2322</idno>
<imprint><date when="2015">2015</date>
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</series>
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<term>Cell Nucleus (metabolism)</term>
<term>Cell Nucleus (virology)</term>
<term>Cytoplasm (metabolism)</term>
<term>Cytoplasm (virology)</term>
<term>DEAD Box Protein 58 (genetics)</term>
<term>DEAD Box Protein 58 (metabolism)</term>
<term>HeLa Cells (virology)</term>
<term>Host-Pathogen Interactions</term>
<term>Humans</term>
<term>I-kappa B Kinase (metabolism)</term>
<term>Interferon Regulatory Factor-3 (genetics)</term>
<term>Interferon Regulatory Factor-3 (metabolism)</term>
<term>Interferon Regulatory Factor-7 (metabolism)</term>
<term>Interferon-Induced Helicase, IFIH1 (genetics)</term>
<term>Interferon-Induced Helicase, IFIH1 (metabolism)</term>
<term>Interferon-beta (genetics)</term>
<term>Interferon-beta (metabolism)</term>
<term>Middle East Respiratory Syndrome Coronavirus (pathogenicity)</term>
<term>Phosphorylation</term>
<term>Protein-Serine-Threonine Kinases (metabolism)</term>
<term>Viral Proteins (genetics)</term>
<term>Viral Proteins (metabolism)</term>
<term>Viral Proteins (pharmacology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Cellules HeLa (virologie)</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (pathogénicité)</term>
<term>Cytoplasme (métabolisme)</term>
<term>Cytoplasme (virologie)</term>
<term>Facteur-3 de régulation d'interféron (génétique)</term>
<term>Facteur-3 de régulation d'interféron (métabolisme)</term>
<term>Facteur-7 de régulation d'interféron (métabolisme)</term>
<term>Humains</term>
<term>Hélicase  IFIH1 inductrice de l'interféron (génétique)</term>
<term>Hélicase  IFIH1 inductrice de l'interféron (métabolisme)</term>
<term>I-kappa B Kinase (métabolisme)</term>
<term>Interactions hôte-pathogène</term>
<term>Interféron bêta (génétique)</term>
<term>Interféron bêta (métabolisme)</term>
<term>Noyau de la cellule (métabolisme)</term>
<term>Noyau de la cellule (virologie)</term>
<term>Phosphorylation</term>
<term>Protein-Serine-Threonine Kinases (métabolisme)</term>
<term>Protéine-58 à domaine DEAD (génétique)</term>
<term>Protéine-58 à domaine DEAD (métabolisme)</term>
<term>Protéines adaptatrices de la transduction du signal (métabolisme)</term>
<term>Protéines virales (génétique)</term>
<term>Protéines virales (métabolisme)</term>
<term>Protéines virales (pharmacologie)</term>
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<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>DEAD Box Protein 58</term>
<term>Interferon Regulatory Factor-3</term>
<term>Interferon-Induced Helicase, IFIH1</term>
<term>Interferon-beta</term>
<term>Viral Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Adaptor Proteins, Signal Transducing</term>
<term>DEAD Box Protein 58</term>
<term>I-kappa B Kinase</term>
<term>Interferon Regulatory Factor-3</term>
<term>Interferon Regulatory Factor-7</term>
<term>Interferon-Induced Helicase, IFIH1</term>
<term>Interferon-beta</term>
<term>Protein-Serine-Threonine Kinases</term>
<term>Viral Proteins</term>
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<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Facteur-3 de régulation d'interféron</term>
<term>Hélicase  IFIH1 inductrice de l'interféron</term>
<term>Interféron bêta</term>
<term>Protéine-58 à domaine DEAD</term>
<term>Protéines virales</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Cell Nucleus</term>
<term>Cytoplasm</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cytoplasme</term>
<term>Facteur-3 de régulation d'interféron</term>
<term>Facteur-7 de régulation d'interféron</term>
<term>Hélicase  IFIH1 inductrice de l'interféron</term>
<term>I-kappa B Kinase</term>
<term>Interféron bêta</term>
<term>Noyau de la cellule</term>
<term>Protein-Serine-Threonine Kinases</term>
<term>Protéine-58 à domaine DEAD</term>
<term>Protéines adaptatrices de la transduction du signal</term>
<term>Protéines virales</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Protéines virales</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Viral Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Cellules HeLa</term>
<term>Cytoplasme</term>
<term>Noyau de la cellule</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Cell Nucleus</term>
<term>Cytoplasm</term>
<term>HeLa Cells</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Host-Pathogen Interactions</term>
<term>Humans</term>
<term>Phosphorylation</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Humains</term>
<term>Interactions hôte-pathogène</term>
<term>Phosphorylation</term>
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<front><div type="abstract" xml:lang="en"><p>Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel and highly pathogenic human coronavirus and has quickly spread to other countries in the Middle East, Europe, North Africa and Asia since 2012. Previous studies have shown that MERS-CoV ORF4b antagonizes the early antiviral alpha/beta interferon (IFN-α/β) response, which may significantly contribute to MERS-CoV pathogenesis; however, the underlying mechanism is poorly understood. Here, we found that ORF4b in the cytoplasm could specifically bind to TANK binding kinase 1 (TBK1) and IκB kinase epsilon (IKKε), suppress the molecular interaction between mitochondrial antiviral signaling protein (MAVS) and IKKε and inhibit IFN regulatory factor 3 (IRF3) phosphorylation and subsequent IFN-β production. Further analysis showed that ORF4b could also inhibit IRF3 and IRF7-induced production of IFN-β, whereas deletion of the nuclear localization signal of ORF4b abrogated its ability to inhibit IRF3 and IRF7-induced production of IFN-β, but not IFN-β production induced by RIG-I, MDA5, MAVS, IKKε and TBK-1, suggesting that ORF4b could inhibit the induction of IFN-β in both the cytoplasm and nucleus. Collectively, these results indicate that MERS-CoV ORF4b inhibits the induction of type I IFN through a direct interaction with IKKε/TBK1 in the cytoplasm and also in the nucleus with unknown mechanism. Viruses have evolved multiple strategies to evade or thwart a host’s antiviral responses. A novel human coronavirus (HCoV), Middle East respiratory syndrome coronavirus (MERS-CoV), is distinguished from other coronaviruses by its high pathogenicity and mortality. However, virulence determinants that distinguish MERS-CoV from other HCoVs have yet to be identified. MERS-CoV ORF4b antagonizes the early antiviral response, which may contribute to MERS-CoV pathogenesis. Here, we report the identification of the interferon (IFN) antagonism mechanism of MERS-CoV ORF4b. MERS-CoV ORF4b inhibits the production of type I IFN through a direct interaction with IKKε/TBK1 in the cytoplasm and also in the nucleus with unknown mechanism. These findings provide a rationale for the novel pathogenesis of MERS-CoV as well as a basis for developing a candidate therapeutic against this virus.</p>
</div>
</front>
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</record>

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EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Main/Curation

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001671 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Main/Curation/biblio.hfd -nk 001671 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Sante
   |area=    MersV1
   |flux=    Main
   |étape=   Curation
   |type=    RBID
   |clé=     PMC:4668369
   |texte=   Middle East respiratory syndrome coronavirus ORF4b protein inhibits type I interferon production through both cytoplasmic and nuclear targets
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Curation/RBID.i   -Sk "pubmed:26631542" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Curation/biblio.hfd   \
       | NlmPubMed2Wicri -a MersV1

This area was generated with Dilib version V0.6.33.
Data generation: Mon Apr 20 23:26:43 2020. Site generation: Sat Mar 27 09:06:09 2021

	Serveur d'exploration MERS
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.

Serveur d'exploration MERS

Middle East respiratory syndrome coronavirus ORF4b protein inhibits type I interferon production through both cytoplasmic and nuclear targets

Middle East respiratory syndrome coronavirus ORF4b protein inhibits type I interferon production through both cytoplasmic and nuclear targets

Source :

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Links toward previous steps (curation, corpus...)

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Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki