Characterization of the antiviral effects of interferon-alpha against a SARS-like coronoavirus infection in vitro.
Identifieur interne : 003F56 ( Main/Exploration ); précédent : 003F55; suivant : 003F57Characterization of the antiviral effects of interferon-alpha against a SARS-like coronoavirus infection in vitro.
Auteurs : Joanna Zorzitto [Canada] ; Carole L. Galligan ; Joanna J M. Ueng ; Eleanor N. FishSource :
- Cell research [ 1001-0602 ] ; 2006.
Descripteurs français
- KwdFr :
- Analyse de profil d'expression de gènes, Animaux, Antienzymes (métabolisme), Antiviraux (immunologie), Antiviraux (usage thérapeutique), Humains, Infections à coronavirus (immunologie), Infections à coronavirus (traitement médicamenteux), Interféron alpha (immunologie), Interféron alpha (usage thérapeutique), Janus kinase 1 (antagonistes et inhibiteurs), Janus kinase 1 (métabolisme), Lignée cellulaire, Protein kinase C-delta (antagonistes et inhibiteurs), Protein kinase C-delta (métabolisme), Souris, Séquençage par oligonucléotides en batterie, Virus de l'hépatite murine (immunologie), Virus du SRAS (immunologie), p38 Mitogen-Activated Protein Kinases (antagonistes et inhibiteurs), p38 Mitogen-Activated Protein Kinases (métabolisme).
- MESH :
- antagonistes et inhibiteurs : Janus kinase 1, Protein kinase C-delta, p38 Mitogen-Activated Protein Kinases.
- immunologie : Antiviraux, Infections à coronavirus, Interféron alpha, Virus de l'hépatite murine, Virus du SRAS.
- métabolisme : Antienzymes, Janus kinase 1, Protein kinase C-delta, p38 Mitogen-Activated Protein Kinases.
- traitement médicamenteux : Infections à coronavirus.
- usage thérapeutique : Antiviraux, Interféron alpha.
- Analyse de profil d'expression de gènes, Animaux, Humains, Lignée cellulaire, Souris, Séquençage par oligonucléotides en batterie.
English descriptors
- KwdEn :
- Animals, Antiviral Agents (immunology), Antiviral Agents (therapeutic use), Cell Line, Coronavirus Infections (drug therapy), Coronavirus Infections (immunology), Enzyme Inhibitors (metabolism), Gene Expression Profiling, Humans, Interferon-alpha (immunology), Interferon-alpha (therapeutic use), Janus Kinase 1 (antagonists & inhibitors), Janus Kinase 1 (metabolism), Mice, Murine hepatitis virus (immunology), Oligonucleotide Array Sequence Analysis, Protein Kinase C-delta (antagonists & inhibitors), Protein Kinase C-delta (metabolism), SARS Virus (immunology), p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors), p38 Mitogen-Activated Protein Kinases (metabolism).
- MESH :
- chemical , antagonists & inhibitors : Janus Kinase 1, Protein Kinase C-delta, p38 Mitogen-Activated Protein Kinases.
- chemical , immunology : Antiviral Agents, Interferon-alpha.
- chemical , metabolism : Enzyme Inhibitors, Janus Kinase 1, Protein Kinase C-delta, p38 Mitogen-Activated Protein Kinases.
- chemical , therapeutic use : Antiviral Agents, Interferon-alpha.
- drug therapy : Coronavirus Infections.
- immunology : Coronavirus Infections, Murine hepatitis virus, SARS Virus.
- Animals, Cell Line, Gene Expression Profiling, Humans, Mice, Oligonucleotide Array Sequence Analysis.
Abstract
Interferon (IFN)-alphas bind to and activate their cognate cell surface receptor to invoke an antiviral response in target cells. Well-described receptor-mediated signaling events result in transcriptional regulation of IFN sensitive genes, effectors of this antiviral response. Results from a pilot study to evaluate the clinical efficacy of IFN-alpha treatment of SARS patients provided evidence for IFN-inducible resolution of disease. In this report we examined the contribution of IFN-inducible phosphorylation-activation of specific signaling effectors to protection from infection by a SARS-related murine coronavirus, MHV-1. As anticipated, the earliest receptor-activation event, Jak1 phosphorylation, is critical for IFN-inducible protection from MHV-1 infection. Additionally, we provide evidence for the contribution of two kinases, the MAP kinase p38MAPK, and protein kinase C (PKC) delta to antiviral protection from MHV-1 infection. Notably, our data suggest that MHV-1 infection, as for the Urbani SARS coronoavirus, inhibits an IFN response, inferred from the lack of activation of pkr and 2'5'-oas, genes associated with mediating the antiviral activities of IFN-alphas. To identify potential target genes that are activated downstream of the IFN-inducible signaling effectors we identified, and that mediate protection from coronavirus infection, we examined the gene expression profiles in the peripheral blood mononuclear cells of SARS patients who received IFN treatment. A subset of differentially regulated genes were distinguished with functional properties associated with antimicrobial activities.
DOI: 10.1038/sj.cr.7310030
PubMed: 16474437
Affiliations:
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Le document en format XML
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Galligan</name></author><author><name sortKey="Ueng, Joanna J M" sort="Ueng, Joanna J M" uniqKey="Ueng J" first="Joanna J M" last="Ueng">Joanna J M. Ueng</name></author><author><name sortKey="Fish, Eleanor N" sort="Fish, Eleanor N" uniqKey="Fish E" first="Eleanor N" last="Fish">Eleanor N. Fish</name></author></analytic><series><title level="j">Cell research</title><idno type="ISSN">1001-0602</idno><imprint><date when="2006" type="published">2006</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antiviral Agents (immunology)</term><term>Antiviral Agents (therapeutic use)</term><term>Cell Line</term><term>Coronavirus Infections (drug therapy)</term><term>Coronavirus Infections (immunology)</term><term>Enzyme Inhibitors (metabolism)</term><term>Gene Expression Profiling</term><term>Humans</term><term>Interferon-alpha (immunology)</term><term>Interferon-alpha (therapeutic use)</term><term>Janus Kinase 1 (antagonists & inhibitors)</term><term>Janus Kinase 1 (metabolism)</term><term>Mice</term><term>Murine hepatitis virus (immunology)</term><term>Oligonucleotide Array Sequence Analysis</term><term>Protein Kinase C-delta (antagonists & inhibitors)</term><term>Protein Kinase C-delta (metabolism)</term><term>SARS Virus (immunology)</term><term>p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors)</term><term>p38 Mitogen-Activated Protein Kinases (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Analyse de profil d'expression de gènes</term><term>Animaux</term><term>Antienzymes (métabolisme)</term><term>Antiviraux (immunologie)</term><term>Antiviraux (usage thérapeutique)</term><term>Humains</term><term>Infections à coronavirus (immunologie)</term><term>Infections à coronavirus (traitement médicamenteux)</term><term>Interféron alpha (immunologie)</term><term>Interféron alpha (usage thérapeutique)</term><term>Janus kinase 1 (antagonistes et inhibiteurs)</term><term>Janus kinase 1 (métabolisme)</term><term>Lignée cellulaire</term><term>Protein kinase C-delta (antagonistes et inhibiteurs)</term><term>Protein kinase C-delta (métabolisme)</term><term>Souris</term><term>Séquençage par oligonucléotides en batterie</term><term>Virus de l'hépatite murine (immunologie)</term><term>Virus du SRAS (immunologie)</term><term>p38 Mitogen-Activated Protein Kinases (antagonistes et inhibiteurs)</term><term>p38 Mitogen-Activated Protein Kinases (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Janus Kinase 1</term><term>Protein Kinase C-delta</term><term>p38 Mitogen-Activated Protein Kinases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antiviral Agents</term><term>Interferon-alpha</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Enzyme Inhibitors</term><term>Janus Kinase 1</term><term>Protein Kinase C-delta</term><term>p38 Mitogen-Activated Protein Kinases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiviral Agents</term><term>Interferon-alpha</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Janus kinase 1</term><term>Protein kinase C-delta</term><term>p38 Mitogen-Activated Protein Kinases</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Antiviraux</term><term>Infections à coronavirus</term><term>Interféron alpha</term><term>Virus de l'hépatite murine</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Coronavirus Infections</term><term>Murine hepatitis virus</term><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Antienzymes</term><term>Janus kinase 1</term><term>Protein kinase C-delta</term><term>p38 Mitogen-Activated Protein Kinases</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infections à coronavirus</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Antiviraux</term><term>Interféron alpha</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line</term><term>Gene Expression Profiling</term><term>Humans</term><term>Mice</term><term>Oligonucleotide Array Sequence Analysis</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Analyse de profil d'expression de gènes</term><term>Animaux</term><term>Humains</term><term>Lignée cellulaire</term><term>Souris</term><term>Séquençage par oligonucléotides en batterie</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Interferon (IFN)-alphas bind to and activate their cognate cell surface receptor to invoke an antiviral response in target cells. Well-described receptor-mediated signaling events result in transcriptional regulation of IFN sensitive genes, effectors of this antiviral response. Results from a pilot study to evaluate the clinical efficacy of IFN-alpha treatment of SARS patients provided evidence for IFN-inducible resolution of disease. In this report we examined the contribution of IFN-inducible phosphorylation-activation of specific signaling effectors to protection from infection by a SARS-related murine coronavirus, MHV-1. As anticipated, the earliest receptor-activation event, Jak1 phosphorylation, is critical for IFN-inducible protection from MHV-1 infection. Additionally, we provide evidence for the contribution of two kinases, the MAP kinase p38MAPK, and protein kinase C (PKC) delta to antiviral protection from MHV-1 infection. Notably, our data suggest that MHV-1 infection, as for the Urbani SARS coronoavirus, inhibits an IFN response, inferred from the lack of activation of pkr and 2'5'-oas, genes associated with mediating the antiviral activities of IFN-alphas. To identify potential target genes that are activated downstream of the IFN-inducible signaling effectors we identified, and that mediate protection from coronavirus infection, we examined the gene expression profiles in the peripheral blood mononuclear cells of SARS patients who received IFN treatment. A subset of differentially regulated genes were distinguished with functional properties associated with antimicrobial activities.</div></front></TEI><affiliations><list><country><li>Canada</li></country><region><li>Ontario</li></region><settlement><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><noCountry><name sortKey="Fish, Eleanor N" sort="Fish, Eleanor N" uniqKey="Fish E" first="Eleanor N" last="Fish">Eleanor N. Fish</name><name sortKey="Galligan, Carole L" sort="Galligan, Carole L" uniqKey="Galligan C" first="Carole L" last="Galligan">Carole L. Galligan</name><name sortKey="Ueng, Joanna J M" sort="Ueng, Joanna J M" uniqKey="Ueng J" first="Joanna J M" last="Ueng">Joanna J M. Ueng</name></noCountry><country name="Canada"><region name="Ontario"><name sortKey="Zorzitto, Joanna" sort="Zorzitto, Joanna" uniqKey="Zorzitto J" first="Joanna" last="Zorzitto">Joanna Zorzitto</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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