Functional genomics highlights differential induction of antiviral pathways in the lungs of SARS-CoV-infected macaques.
Identifieur interne : 003701 ( Main/Exploration ); précédent : 003700; suivant : 003702Functional genomics highlights differential induction of antiviral pathways in the lungs of SARS-CoV-infected macaques.
Auteurs : Anna De Lang [Pays-Bas] ; Tracey Baas ; Thomas Teal ; Lonneke M. Leijten ; Brandon Rain ; Albert D. Osterhaus ; Bart L. Haagmans ; Michael G. KatzeSource :
- PLoS pathogens [ 1553-7374 ] ; 2007.
Descripteurs français
- KwdFr :
- Analyse de profil d'expression de gènes, Animaux, Cytokines (génétique), Cytokines (métabolisme), Facteur de transcription STAT-1 (métabolisme), Génomique, Immunohistochimie, Interféron de type I (biosynthèse), Interféron de type I (génétique), Macaca fascicularis, Marqueurs biologiques (métabolisme), Modèles animaux de maladie humaine, Poumon (anatomopathologie), Poumon (immunologie), Poumon (virologie), Régulation de l'expression des gènes viraux, Réplication virale, Syndrome respiratoire aigu sévère (anatomopathologie), Syndrome respiratoire aigu sévère (métabolisme), Syndrome respiratoire aigu sévère (virologie), Séquençage par oligonucléotides en batterie, Virus du SRAS (génétique), Virus du SRAS (pathogénicité).
- MESH :
- anatomopathologie : Poumon, Syndrome respiratoire aigu sévère.
- biosynthèse : Interféron de type I.
- génétique : Cytokines, Interféron de type I, Virus du SRAS.
- immunologie : Poumon.
- métabolisme : Cytokines, Facteur de transcription STAT-1, Marqueurs biologiques, Syndrome respiratoire aigu sévère.
- pathogénicité : Virus du SRAS.
- virologie : Poumon, Syndrome respiratoire aigu sévère.
- Analyse de profil d'expression de gènes, Animaux, Génomique, Immunohistochimie, Macaca fascicularis, Modèles animaux de maladie humaine, Régulation de l'expression des gènes viraux, Réplication virale, Séquençage par oligonucléotides en batterie.
English descriptors
- KwdEn :
- Animals, Biomarkers (metabolism), Cytokines (genetics), Cytokines (metabolism), Disease Models, Animal, Gene Expression Profiling, Gene Expression Regulation, Viral, Genomics, Immunohistochemistry, Interferon Type I (biosynthesis), Interferon Type I (genetics), Lung (immunology), Lung (pathology), Lung (virology), Macaca fascicularis, Oligonucleotide Array Sequence Analysis, SARS Virus (genetics), SARS Virus (pathogenicity), STAT1 Transcription Factor (metabolism), Severe Acute Respiratory Syndrome (metabolism), Severe Acute Respiratory Syndrome (pathology), Severe Acute Respiratory Syndrome (virology), Virus Replication.
- MESH :
- chemical , biosynthesis : Interferon Type I.
- chemical , genetics : Cytokines, Interferon Type I.
- chemical , metabolism : Biomarkers, Cytokines, STAT1 Transcription Factor.
- genetics : SARS Virus.
- immunology : Lung.
- metabolism : Severe Acute Respiratory Syndrome.
- pathogenicity : SARS Virus.
- pathology : Lung, Severe Acute Respiratory Syndrome.
- virology : Lung, Severe Acute Respiratory Syndrome.
- Animals, Disease Models, Animal, Gene Expression Profiling, Gene Expression Regulation, Viral, Genomics, Immunohistochemistry, Macaca fascicularis, Oligonucleotide Array Sequence Analysis, Virus Replication.
Abstract
The pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV) is likely mediated by disproportional immune responses and the ability of the virus to circumvent innate immunity. Using functional genomics, we analyzed early host responses to SARS-CoV infection in the lungs of adolescent cynomolgus macaques (Macaca fascicularis) that show lung pathology similar to that observed in human adults with SARS. Analysis of gene signatures revealed induction of a strong innate immune response characterized by the stimulation of various cytokine and chemokine genes, including interleukin (IL)-6, IL-8, and IP-10, which corresponds to the host response seen in acute respiratory distress syndrome. As opposed to many in vitro experiments, SARS-CoV induced a wide range of type I interferons (IFNs) and nuclear translocation of phosphorylated signal transducer and activator of transcription 1 in the lungs of macaques. Using immunohistochemistry, we revealed that these antiviral signaling pathways were differentially regulated in distinctive subsets of cells. Our studies emphasize that the induction of early IFN signaling may be critical to confer protection against SARS-CoV infection and highlight the strength of combining functional genomics with immunohistochemistry to further unravel the pathogenesis of SARS.
DOI: 10.1371/journal.ppat.0030112
PubMed: 17696609
Affiliations:
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Le document en format XML
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<term>Cytokines (metabolism)</term>
<term>Disease Models, Animal</term>
<term>Gene Expression Profiling</term>
<term>Gene Expression Regulation, Viral</term>
<term>Genomics</term>
<term>Immunohistochemistry</term>
<term>Interferon Type I (biosynthesis)</term>
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<term>Lung (pathology)</term>
<term>Lung (virology)</term>
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<term>Oligonucleotide Array Sequence Analysis</term>
<term>SARS Virus (genetics)</term>
<term>SARS Virus (pathogenicity)</term>
<term>STAT1 Transcription Factor (metabolism)</term>
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<term>Virus Replication</term>
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<term>Facteur de transcription STAT-1 (métabolisme)</term>
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<term>Modèles animaux de maladie humaine</term>
<term>Poumon (anatomopathologie)</term>
<term>Poumon (immunologie)</term>
<term>Poumon (virologie)</term>
<term>Régulation de l'expression des gènes viraux</term>
<term>Réplication virale</term>
<term>Syndrome respiratoire aigu sévère (anatomopathologie)</term>
<term>Syndrome respiratoire aigu sévère (métabolisme)</term>
<term>Syndrome respiratoire aigu sévère (virologie)</term>
<term>Séquençage par oligonucléotides en batterie</term>
<term>Virus du SRAS (génétique)</term>
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<term>Facteur de transcription STAT-1</term>
<term>Marqueurs biologiques</term>
<term>Syndrome respiratoire aigu sévère</term>
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<term>Macaca fascicularis</term>
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<front><div type="abstract" xml:lang="en">The pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV) is likely mediated by disproportional immune responses and the ability of the virus to circumvent innate immunity. Using functional genomics, we analyzed early host responses to SARS-CoV infection in the lungs of adolescent cynomolgus macaques (Macaca fascicularis) that show lung pathology similar to that observed in human adults with SARS. Analysis of gene signatures revealed induction of a strong innate immune response characterized by the stimulation of various cytokine and chemokine genes, including interleukin (IL)-6, IL-8, and IP-10, which corresponds to the host response seen in acute respiratory distress syndrome. As opposed to many in vitro experiments, SARS-CoV induced a wide range of type I interferons (IFNs) and nuclear translocation of phosphorylated signal transducer and activator of transcription 1 in the lungs of macaques. Using immunohistochemistry, we revealed that these antiviral signaling pathways were differentially regulated in distinctive subsets of cells. Our studies emphasize that the induction of early IFN signaling may be critical to confer protection against SARS-CoV infection and highlight the strength of combining functional genomics with immunohistochemistry to further unravel the pathogenesis of SARS.</div>
</front>
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<tree><noCountry><name sortKey="Baas, Tracey" sort="Baas, Tracey" uniqKey="Baas T" first="Tracey" last="Baas">Tracey Baas</name>
<name sortKey="Haagmans, Bart L" sort="Haagmans, Bart L" uniqKey="Haagmans B" first="Bart L" last="Haagmans">Bart L. Haagmans</name>
<name sortKey="Katze, Michael G" sort="Katze, Michael G" uniqKey="Katze M" first="Michael G" last="Katze">Michael G. Katze</name>
<name sortKey="Leijten, Lonneke M" sort="Leijten, Lonneke M" uniqKey="Leijten L" first="Lonneke M" last="Leijten">Lonneke M. Leijten</name>
<name sortKey="Osterhaus, Albert D" sort="Osterhaus, Albert D" uniqKey="Osterhaus A" first="Albert D" last="Osterhaus">Albert D. Osterhaus</name>
<name sortKey="Rain, Brandon" sort="Rain, Brandon" uniqKey="Rain B" first="Brandon" last="Rain">Brandon Rain</name>
<name sortKey="Teal, Thomas" sort="Teal, Thomas" uniqKey="Teal T" first="Thomas" last="Teal">Thomas Teal</name>
</noCountry>
<country name="Pays-Bas"><region name="Hollande-Méridionale"><name sortKey="De Lang, Anna" sort="De Lang, Anna" uniqKey="De Lang A" first="Anna" last="De Lang">Anna De Lang</name>
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