SARS-CoV-Encoded Small RNAs Contribute to Infection-Associated Lung Pathology
Identifieur interne : 002D68 ( Ncbi/Curation ); précédent : 002D67; suivant : 002D69SARS-CoV-Encoded Small RNAs Contribute to Infection-Associated Lung Pathology
Auteurs : Lucía Morales [Espagne] ; Juan Carlos Oliveros [Espagne] ; Raúl Fernandez-Delgado [Espagne] ; Benjamin Robert Tenoever [États-Unis] ; Luis Enjuanes [Espagne] ; Isabel Sola [Espagne]Source :
- Cell Host & Microbe [ 1931-3128 ] ; 2017.
Descripteurs français
- KwdFr :
- ARN viral (génétique), ARN viral (métabolisme), Animaux, Cytokines (biosynthèse), Modèles animaux de maladie humaine, Petit ARN non traduit (génétique), Petit ARN non traduit (métabolisme), Poumon (anatomopathologie), Souris, Syndrome respiratoire aigu sévère (anatomopathologie), Syndrome respiratoire aigu sévère (virologie), Séquençage nucléotidique à haut débit, Virus du SRAS (pathogénicité).
- MESH :
- anatomopathologie : Poumon, Syndrome respiratoire aigu sévère.
- biosynthèse : Cytokines.
- génétique : ARN viral, Petit ARN non traduit.
- métabolisme : ARN viral, Petit ARN non traduit.
- pathogénicité : Virus du SRAS.
- virologie : Syndrome respiratoire aigu sévère.
- Animaux, Modèles animaux de maladie humaine, Souris, Séquençage nucléotidique à haut débit.
English descriptors
- KwdEn :
- Animals, Cytokines (biosynthesis), Disease Models, Animal, High-Throughput Nucleotide Sequencing, Lung (pathology), Mice, RNA, Small Untranslated (genetics), RNA, Small Untranslated (metabolism), RNA, Viral (genetics), RNA, Viral (metabolism), SARS Virus (pathogenicity), Severe Acute Respiratory Syndrome (pathology), Severe Acute Respiratory Syndrome (virology).
- MESH :
- chemical , biosynthesis : Cytokines.
- chemical , genetics : RNA, Small Untranslated, RNA, Viral.
- chemical , metabolism : RNA, Small Untranslated, RNA, Viral.
- pathogenicity : SARS Virus.
- pathology : Lung, Severe Acute Respiratory Syndrome.
- virology : Severe Acute Respiratory Syndrome.
- Animals, Disease Models, Animal, High-Throughput Nucleotide Sequencing, Mice.
Abstract
Severe acute respiratory syndrome coronavirus (SARS-CoV) causes lethal disease in humans, which is characterized by exacerbated inflammatory response and extensive lung pathology. To address the relevance of small non-coding RNAs in SARS-CoV pathology, we deep sequenced RNAs from the lungs of infected mice and discovered three 18–22 nt small viral RNAs (svRNAs). The three svRNAs were derived from the nsp3 (svRNA-nsp3.1 and -nsp3.2) and N (svRNA-N) genomic regions of SARS-CoV. Biogenesis of CoV svRNAs was RNase III, cell type, and host species independent, but it was dependent on the extent of viral replication. Antagomir-mediated inhibition of svRNA-N significantly reduced in vivo lung pathology and pro-inflammatory cytokine expression. Taken together, these data indicate that svRNAs contribute to SARS-CoV pathogenesis and highlight the potential of svRNA-N antagomirs as antivirals.
Url:
DOI: 10.1016/j.chom.2017.01.015
PubMed: 28216251
PubMed Central: 5662013
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PMC:5662013Le document en format XML
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<series><title level="j">Cell Host & Microbe</title>
<idno type="ISSN">1931-3128</idno>
<idno type="eISSN">1934-6069</idno>
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<term>Cytokines (biosynthesis)</term>
<term>Disease Models, Animal</term>
<term>High-Throughput Nucleotide Sequencing</term>
<term>Lung (pathology)</term>
<term>Mice</term>
<term>RNA, Small Untranslated (genetics)</term>
<term>RNA, Small Untranslated (metabolism)</term>
<term>RNA, Viral (genetics)</term>
<term>RNA, Viral (metabolism)</term>
<term>SARS Virus (pathogenicity)</term>
<term>Severe Acute Respiratory Syndrome (pathology)</term>
<term>Severe Acute Respiratory Syndrome (virology)</term>
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<term>ARN viral (métabolisme)</term>
<term>Animaux</term>
<term>Cytokines (biosynthèse)</term>
<term>Modèles animaux de maladie humaine</term>
<term>Petit ARN non traduit (génétique)</term>
<term>Petit ARN non traduit (métabolisme)</term>
<term>Poumon (anatomopathologie)</term>
<term>Souris</term>
<term>Syndrome respiratoire aigu sévère (anatomopathologie)</term>
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<term>RNA, Viral</term>
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<term>RNA, Viral</term>
</keywords>
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<term>Syndrome respiratoire aigu sévère</term>
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<front><div type="abstract" xml:lang="en"><title>Summary</title>
<p>Severe acute respiratory syndrome coronavirus (SARS-CoV) causes lethal disease in humans, which is characterized by exacerbated inflammatory response and extensive lung pathology. To address the relevance of small non-coding RNAs in SARS-CoV pathology, we deep sequenced RNAs from the lungs of infected mice and discovered three 18–22 nt small viral RNAs (svRNAs). The three svRNAs were derived from the nsp3 (svRNA-nsp3.1 and -nsp3.2) and N (svRNA-N) genomic regions of SARS-CoV. Biogenesis of CoV svRNAs was RNase III, cell type, and host species independent, but it was dependent on the extent of viral replication. Antagomir-mediated inhibition of svRNA-N significantly reduced in vivo lung pathology and pro-inflammatory cytokine expression. Taken together, these data indicate that svRNAs contribute to SARS-CoV pathogenesis and highlight the potential of svRNA-N antagomirs as antivirals.</p>
</div>
</front>
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