Mechanisms of Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury
Identifieur interne : 001902 ( Main/Exploration ); précédent : 001901; suivant : 001903Mechanisms of Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury
Auteurs : Lisa E. Gralinski ; Armand Bankhead ; Sophia Jeng ; Vineet D. Menachery ; Sean Proll ; Sarah E. Belisle ; Melissa Matzke ; Bobbie-Jo M. Webb-Robertson ; Maria L. Luna ; Anil K. Shukla ; Martin T. Ferris ; Meagan Bolles ; Jean Chang ; Lauri Aicher ; Katrina M. Waters ; Richard D. Smith ; Thomas O. Metz ; G. Lynn Law ; Michael G. Katze ; Shannon Mcweeney ; Ralph S. BaricSource :
- mBio [ 2150-7511 ] ; 2013.
Descripteurs français
- KwdFr :
- Activateur du plasminogène de type urokinase (génétique), Activateur du plasminogène de type urokinase (métabolisme), Analyse de profil d'expression de gènes, Animaux, Coagulation sanguine, Facteurs temps, Fibrinolyse, Interactions hôte-pathogène, Lésion pulmonaire aigüe (anatomopathologie), Lésion pulmonaire aigüe (virologie), Modèles animaux de maladie humaine, Poumon (anatomopathologie), Poumon (virologie), Protéome (analyse), Souris, Souris de lignée C57BL, Souris knockout, Virus du SRAS (pathogénicité).
- MESH :
- analyse : Protéome.
- anatomopathologie : Lésion pulmonaire aigüe, Poumon.
- génétique : Activateur du plasminogène de type urokinase.
- métabolisme : Activateur du plasminogène de type urokinase.
- pathogénicité : Virus du SRAS.
- virologie : Lésion pulmonaire aigüe, Poumon.
- Analyse de profil d'expression de gènes, Animaux, Coagulation sanguine, Facteurs temps, Fibrinolyse, Interactions hôte-pathogène, Modèles animaux de maladie humaine, Souris, Souris de lignée C57BL, Souris knockout.
English descriptors
- KwdEn :
- Acute Lung Injury (pathology), Acute Lung Injury (virology), Animals, Blood Coagulation, Disease Models, Animal, Fibrinolysis, Gene Expression Profiling, Host-Pathogen Interactions, Lung (pathology), Lung (virology), Mice, Mice, Inbred C57BL, Mice, Knockout, Proteome (analysis), SARS Virus (pathogenicity), Time Factors, Urokinase-Type Plasminogen Activator (genetics), Urokinase-Type Plasminogen Activator (metabolism).
- MESH :
- chemical , analysis : Proteome.
- chemical , genetics : Urokinase-Type Plasminogen Activator.
- chemical , metabolism : Urokinase-Type Plasminogen Activator.
- pathogenicity : SARS Virus.
- pathology : Acute Lung Injury, Lung.
- virology : Acute Lung Injury, Lung.
- Animals, Blood Coagulation, Disease Models, Animal, Fibrinolysis, Gene Expression Profiling, Host-Pathogen Interactions, Mice, Mice, Inbred C57BL, Mice, Knockout, Time Factors.
Abstract
Systems biology offers considerable promise in uncovering novel pathways by which viruses and other microbial pathogens interact with host signaling and expression networks to mediate disease severity. In this study, we have developed an unbiased modeling approach to identify new pathways and network connections mediating acute lung injury, using severe acute respiratory syndrome coronavirus (SARS-CoV) as a model pathogen. We utilized a time course of matched virologic, pathological, and transcriptomic data within a novel methodological framework that can detect pathway enrichment among key highly connected network genes. This unbiased approach produced a high-priority list of 4 genes in one pathway out of over 3,500 genes that were differentially expressed following SARS-CoV infection. With these data, we predicted that the urokinase and other wound repair pathways would regulate lethal versus sublethal disease following SARS-CoV infection in mice. We validated the importance of the urokinase pathway for SARS-CoV disease severity using genetically defined knockout mice, proteomic correlates of pathway activation, and pathological disease severity. The results of these studies demonstrate that a fine balance exists between host coagulation and fibrinolysin pathways regulating pathological disease outcomes, including diffuse alveolar damage and acute lung injury, following infection with highly pathogenic respiratory viruses, such as SARS-CoV.
Url:
DOI: 10.1128/mBio.00271-13
PubMed: 23919993
PubMed Central: 3747576
Affiliations:
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Le document en format XML
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Shukla</name><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author><author><name sortKey="Ferris, Martin T" sort="Ferris, Martin T" uniqKey="Ferris M" first="Martin T." last="Ferris">Martin T. Ferris</name><affiliation><nlm:aff id="aff5"></nlm:aff></affiliation></author><author><name sortKey="Bolles, Meagan" sort="Bolles, Meagan" uniqKey="Bolles M" first="Meagan" last="Bolles">Meagan Bolles</name><affiliation><nlm:aff id="aff6"></nlm:aff></affiliation></author><author><name sortKey="Chang, Jean" sort="Chang, Jean" uniqKey="Chang J" first="Jean" last="Chang">Jean Chang</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Aicher, Lauri" sort="Aicher, Lauri" uniqKey="Aicher L" first="Lauri" last="Aicher">Lauri Aicher</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Waters, Katrina M" sort="Waters, Katrina M" uniqKey="Waters K" first="Katrina M." last="Waters">Katrina M. Waters</name><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author><author><name sortKey="Smith, Richard D" sort="Smith, Richard D" uniqKey="Smith R" first="Richard D." last="Smith">Richard D. Smith</name><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author><author><name sortKey="Metz, Thomas O" sort="Metz, Thomas O" uniqKey="Metz T" first="Thomas O." last="Metz">Thomas O. Metz</name><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author><author><name sortKey="Law, G Lynn" sort="Law, G Lynn" uniqKey="Law G" first="G. Lynn" last="Law">G. Lynn Law</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Katze, Michael G" sort="Katze, Michael G" uniqKey="Katze M" first="Michael G." last="Katze">Michael G. Katze</name></author><author><name sortKey="Mcweeney, Shannon" sort="Mcweeney, Shannon" uniqKey="Mcweeney S" first="Shannon" last="Mcweeney">Shannon Mcweeney</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name></author></analytic><series><title level="j">mBio</title><idno type="eISSN">2150-7511</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acute Lung Injury (pathology)</term><term>Acute Lung Injury (virology)</term><term>Animals</term><term>Blood Coagulation</term><term>Disease Models, Animal</term><term>Fibrinolysis</term><term>Gene Expression Profiling</term><term>Host-Pathogen Interactions</term><term>Lung (pathology)</term><term>Lung (virology)</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Knockout</term><term>Proteome (analysis)</term><term>SARS Virus (pathogenicity)</term><term>Time Factors</term><term>Urokinase-Type Plasminogen Activator (genetics)</term><term>Urokinase-Type Plasminogen Activator (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Activateur du plasminogène de type urokinase (génétique)</term><term>Activateur du plasminogène de type urokinase (métabolisme)</term><term>Analyse de profil d'expression de gènes</term><term>Animaux</term><term>Coagulation sanguine</term><term>Facteurs temps</term><term>Fibrinolyse</term><term>Interactions hôte-pathogène</term><term>Lésion pulmonaire aigüe (anatomopathologie)</term><term>Lésion pulmonaire aigüe (virologie)</term><term>Modèles animaux de maladie humaine</term><term>Poumon (anatomopathologie)</term><term>Poumon (virologie)</term><term>Protéome (analyse)</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Souris knockout</term><term>Virus du SRAS (pathogénicité)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Proteome</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Urokinase-Type Plasminogen Activator</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Urokinase-Type Plasminogen Activator</term></keywords><keywords scheme="MESH" qualifier="analyse" xml:lang="fr"><term>Protéome</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Lésion pulmonaire aigüe</term><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Activateur du plasminogène de type urokinase</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Activateur du plasminogène de type urokinase</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Acute Lung Injury</term><term>Lung</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Lésion pulmonaire aigüe</term><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Acute Lung Injury</term><term>Lung</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Blood Coagulation</term><term>Disease Models, Animal</term><term>Fibrinolysis</term><term>Gene Expression Profiling</term><term>Host-Pathogen Interactions</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Knockout</term><term>Time Factors</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Analyse de profil d'expression de gènes</term><term>Animaux</term><term>Coagulation sanguine</term><term>Facteurs temps</term><term>Fibrinolyse</term><term>Interactions hôte-pathogène</term><term>Modèles animaux de maladie humaine</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Souris knockout</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>ABSTRACT</title><p>Systems biology offers considerable promise in uncovering novel pathways by which viruses and other microbial pathogens interact with host signaling and expression networks to mediate disease severity. In this study, we have developed an unbiased modeling approach to identify new pathways and network connections mediating acute lung injury, using severe acute respiratory syndrome coronavirus (SARS-CoV) as a model pathogen. We utilized a time course of matched virologic, pathological, and transcriptomic data within a novel methodological framework that can detect pathway enrichment among key highly connected network genes. This unbiased approach produced a high-priority list of 4 genes in one pathway out of over 3,500 genes that were differentially expressed following SARS-CoV infection. With these data, we predicted that the urokinase and other wound repair pathways would regulate lethal versus sublethal disease following SARS-CoV infection in mice. We validated the importance of the urokinase pathway for SARS-CoV disease severity using genetically defined knockout mice, proteomic correlates of pathway activation, and pathological disease severity. The results of these studies demonstrate that a fine balance exists between host coagulation and fibrinolysin pathways regulating pathological disease outcomes, including diffuse alveolar damage and acute lung injury, following infection with highly pathogenic respiratory viruses, such as SARS-CoV.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Ksiazek, Tg" uniqKey="Ksiazek T">TG Ksiazek</name></author><author><name sortKey="Erdman, D" uniqKey="Erdman D">D Erdman</name></author><author><name sortKey="Goldsmith, Cs" uniqKey="Goldsmith C">CS Goldsmith</name></author><author><name sortKey="Zaki, Sr" uniqKey="Zaki S">SR Zaki</name></author><author><name sortKey="Peret, T" uniqKey="Peret T">T Peret</name></author><author><name sortKey="Emery, S" uniqKey="Emery S">S Emery</name></author><author><name sortKey="Tong, S" uniqKey="Tong S">S Tong</name></author><author><name sortKey="Urbani, C" uniqKey="Urbani C">C 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Baric</name><name sortKey="Belisle, Sarah E" sort="Belisle, Sarah E" uniqKey="Belisle S" first="Sarah E." last="Belisle">Sarah E. Belisle</name><name sortKey="Bolles, Meagan" sort="Bolles, Meagan" uniqKey="Bolles M" first="Meagan" last="Bolles">Meagan Bolles</name><name sortKey="Chang, Jean" sort="Chang, Jean" uniqKey="Chang J" first="Jean" last="Chang">Jean Chang</name><name sortKey="Ferris, Martin T" sort="Ferris, Martin T" uniqKey="Ferris M" first="Martin T." last="Ferris">Martin T. Ferris</name><name sortKey="Gralinski, Lisa E" sort="Gralinski, Lisa E" uniqKey="Gralinski L" first="Lisa E." last="Gralinski">Lisa E. Gralinski</name><name sortKey="Jeng, Sophia" sort="Jeng, Sophia" uniqKey="Jeng S" first="Sophia" last="Jeng">Sophia Jeng</name><name sortKey="Katze, Michael G" sort="Katze, Michael G" uniqKey="Katze M" first="Michael G." last="Katze">Michael G. Katze</name><name sortKey="Law, G Lynn" sort="Law, G Lynn" uniqKey="Law G" first="G. Lynn" last="Law">G. Lynn Law</name><name sortKey="Luna, Maria L" sort="Luna, Maria L" uniqKey="Luna M" first="Maria L." last="Luna">Maria L. Luna</name><name sortKey="Matzke, Melissa" sort="Matzke, Melissa" uniqKey="Matzke M" first="Melissa" last="Matzke">Melissa Matzke</name><name sortKey="Mcweeney, Shannon" sort="Mcweeney, Shannon" uniqKey="Mcweeney S" first="Shannon" last="Mcweeney">Shannon Mcweeney</name><name sortKey="Menachery, Vineet D" sort="Menachery, Vineet D" uniqKey="Menachery V" first="Vineet D." last="Menachery">Vineet D. Menachery</name><name sortKey="Metz, Thomas O" sort="Metz, Thomas O" uniqKey="Metz T" first="Thomas O." last="Metz">Thomas O. Metz</name><name sortKey="Proll, Sean" sort="Proll, Sean" uniqKey="Proll S" first="Sean" last="Proll">Sean Proll</name><name sortKey="Shukla, Anil K" sort="Shukla, Anil K" uniqKey="Shukla A" first="Anil K." last="Shukla">Anil K. Shukla</name><name sortKey="Smith, Richard D" sort="Smith, Richard D" uniqKey="Smith R" first="Richard D." last="Smith">Richard D. Smith</name><name sortKey="Waters, Katrina M" sort="Waters, Katrina M" uniqKey="Waters K" first="Katrina M." last="Waters">Katrina M. Waters</name><name sortKey="Webb Robertson, Bobbie Jo M" sort="Webb Robertson, Bobbie Jo M" uniqKey="Webb Robertson B" first="Bobbie-Jo M." last="Webb-Robertson">Bobbie-Jo M. Webb-Robertson</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Main/Exploration
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Ou
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Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= SrasV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= PMC:3747576
|texte= Mechanisms of Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury
}}
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| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
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