SrasV1, Main, Exploration, bibRecord, 000F88

Middle East Respiratory Syndrome Coronavirus NS4b Protein Inhibits Host RNase L Activation.

Identifieur interne : 000F88 ( Main/Exploration ); précédent : 000F87; suivant : 000F89

Middle East Respiratory Syndrome Coronavirus NS4b Protein Inhibits Host RNase L Activation.

Auteurs : Joshua M. Thornbrough [États-Unis] ; Babal K. Jha [États-Unis] ; Boyd Yount [États-Unis] ; Stephen A. Goldstein [États-Unis] ; Yize Li [États-Unis] ; Ruth Elliott [États-Unis] ; Amy C. Sims [États-Unis] ; Ralph S. Baric [États-Unis] ; Robert H. Silverman [États-Unis] ; Susan R. Weiss [États-Unis]

Source :

mBio [ 2150-7511 ] ; 2016.

RBID : pubmed:27025250

Descripteurs français

KwdFr :
- Animaux, Coronavirus du syndrome respiratoire du Moyen-Orient (physiologie), Cricetinae, Endoribonucleases (antagonistes et inhibiteurs), Humains, Interactions hôte-pathogène, Nucléotides adényliques (métabolisme), Oligoribonucléotides (métabolisme), Protéines virales non structurales (génétique), Protéines virales non structurales (métabolisme), Signaux de localisation nucléaire, Souris, Échappement immunitaire.
MESH :
- antagonistes et inhibiteurs : Endoribonucleases.
- génétique : Protéines virales non structurales.
- métabolisme : Nucléotides adényliques, Oligoribonucléotides, Protéines virales non structurales.
- physiologie : Coronavirus du syndrome respiratoire du Moyen-Orient.
- Animaux, Cricetinae, Humains, Interactions hôte-pathogène, Signaux de localisation nucléaire, Souris, Échappement immunitaire.

English descriptors

KwdEn :
- Adenine Nucleotides (metabolism), Animals, Cricetinae, Endoribonucleases (antagonists & inhibitors), Host-Pathogen Interactions, Humans, Immune Evasion, Mice, Middle East Respiratory Syndrome Coronavirus (physiology), Nuclear Localization Signals, Oligoribonucleotides (metabolism), Viral Nonstructural Proteins (genetics), Viral Nonstructural Proteins (metabolism).
MESH :
- chemical , antagonists & inhibitors : Endoribonucleases.
- chemical , genetics : Viral Nonstructural Proteins.
- chemical , metabolism : Adenine Nucleotides, Oligoribonucleotides, Viral Nonstructural Proteins.
- physiology : Middle East Respiratory Syndrome Coronavirus.
- Animals, Cricetinae, Host-Pathogen Interactions, Humans, Immune Evasion, Mice, Nuclear Localization Signals.

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is the first highly pathogenic human coronavirus to emerge since severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002. Like many coronaviruses, MERS-CoV carries genes that encode multiple accessory proteins that are not required for replication of the genome but are likely involved in pathogenesis. Evasion of host innate immunity through interferon (IFN) antagonism is a critical component of viral pathogenesis. The IFN-inducible oligoadenylate synthetase (OAS)-RNase L pathway activates upon sensing of viral double-stranded RNA (dsRNA). Activated RNase L cleaves viral and host single-stranded RNA (ssRNA), which leads to translational arrest and subsequent cell death, preventing viral replication and spread. Here we report that MERS-CoV, a lineage CBetacoronavirus, and related bat CoV NS4b accessory proteins have phosphodiesterase (PDE) activity and antagonize OAS-RNase L by enzymatically degrading 2',5'-oligoadenylate (2-5A), activators of RNase L. This is a novel function for NS4b, which has previously been reported to antagonize IFN signaling. NS4b proteins are distinct from lineage ABetacoronavirusPDEs and rotavirus gene-encoded PDEs, in having an amino-terminal nuclear localization signal (NLS) and are localized mostly to the nucleus. However, the expression level of cytoplasmic MERS-CoV NS4b protein is sufficient to prevent activation of RNase L. Finally, this is the first report of an RNase L antagonist expressed by a human or bat coronavirus and provides a specific mechanism by which this occurs. Our findings provide a potential mechanism for evasion of innate immunity by MERS-CoV while also identifying a potential target for therapeutic intervention.

DOI: 10.1128/mBio.00258-16
PubMed: 27025250

Affiliations:

Le document en format XML

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<front><div type="abstract" xml:lang="en">Middle East respiratory syndrome coronavirus (MERS-CoV) is the first highly pathogenic human coronavirus to emerge since severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002. Like many coronaviruses, MERS-CoV carries genes that encode multiple accessory proteins that are not required for replication of the genome but are likely involved in pathogenesis. Evasion of host innate immunity through interferon (IFN) antagonism is a critical component of viral pathogenesis. The IFN-inducible oligoadenylate synthetase (OAS)-RNase L pathway activates upon sensing of viral double-stranded RNA (dsRNA). Activated RNase L cleaves viral and host single-stranded RNA (ssRNA), which leads to translational arrest and subsequent cell death, preventing viral replication and spread. Here we report that MERS-CoV, a lineage CBetacoronavirus, and related bat CoV NS4b accessory proteins have phosphodiesterase (PDE) activity and antagonize OAS-RNase L by enzymatically degrading 2',5'-oligoadenylate (2-5A), activators of RNase L. This is a novel function for NS4b, which has previously been reported to antagonize IFN signaling. NS4b proteins are distinct from lineage ABetacoronavirusPDEs and rotavirus gene-encoded PDEs, in having an amino-terminal nuclear localization signal (NLS) and are localized mostly to the nucleus. However, the expression level of cytoplasmic MERS-CoV NS4b protein is sufficient to prevent activation of RNase L. Finally, this is the first report of an RNase L antagonist expressed by a human or bat coronavirus and provides a specific mechanism by which this occurs. Our findings provide a potential mechanism for evasion of innate immunity by MERS-CoV while also identifying a potential target for therapeutic intervention.</div>
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   |type=    RBID
   |clé=     pubmed:27025250
   |texte=   Middle East Respiratory Syndrome Coronavirus NS4b Protein Inhibits Host RNase L Activation.
}}

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HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i   -Sk "pubmed:27025250" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd   \
       | NlmPubMed2Wicri -a SrasV1

This area was generated with Dilib version V0.6.33.
Data generation: Tue Apr 28 14:49:16 2020. Site generation: Sat Mar 27 22:06:49 2021

Serveur d'exploration SRAS

Middle East Respiratory Syndrome Coronavirus NS4b Protein Inhibits Host RNase L Activation.

Middle East Respiratory Syndrome Coronavirus NS4b Protein Inhibits Host RNase L Activation.

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	Serveur d'exploration SRAS
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