Interferon-gamma and interleukin-4 downregulate expression of the SARS coronavirus receptor ACE2 in Vero E6 cells.
Identifieur interne : 003E39 ( Main/Curation ); précédent : 003E38; suivant : 003E40Interferon-gamma and interleukin-4 downregulate expression of the SARS coronavirus receptor ACE2 in Vero E6 cells.
Auteurs : Anna De Lang [Pays-Bas] ; Albert D M E. Osterhaus ; Bart L. HaagmansSource :
- Virology [ 0042-6822 ] ; 2006.
Descripteurs français
- KwdFr :
- Animaux, Antiviraux (pharmacologie), Cellules Vero (), Cellules Vero (métabolisme), Facteurs temps, Interféron gamma (pharmacologie), Interleukine-4 (pharmacologie), Relation dose-effet des médicaments, Récepteurs viraux (), Récepteurs viraux (métabolisme), Régulation négative, Réplication virale (), Syndrome respiratoire aigu sévère (virologie), Virus du SRAS (physiologie).
- MESH :
- métabolisme : Cellules Vero, Récepteurs viraux.
- pharmacologie : Antiviraux, Interféron gamma, Interleukine-4.
- physiologie : Virus du SRAS.
- virologie : Syndrome respiratoire aigu sévère.
- Animaux, Cellules Vero, Facteurs temps, Relation dose-effet des médicaments, Récepteurs viraux, Régulation négative, Réplication virale.
English descriptors
- KwdEn :
- Animals, Antiviral Agents (pharmacology), Chlorocebus aethiops, Dose-Response Relationship, Drug, Down-Regulation, Interferon-gamma (pharmacology), Interleukin-4 (pharmacology), Receptors, Virus (drug effects), Receptors, Virus (metabolism), SARS Virus (physiology), Severe Acute Respiratory Syndrome (virology), Time Factors, Vero Cells (drug effects), Vero Cells (metabolism), Virus Replication (drug effects).
- MESH :
- chemical , drug effects : Receptors, Virus.
- chemical , metabolism : Receptors, Virus.
- chemical , pharmacology : Antiviral Agents, Interferon-gamma, Interleukin-4.
- drug effects : Vero Cells, Virus Replication.
- metabolism : Vero Cells.
- physiology : SARS Virus.
- virology : Severe Acute Respiratory Syndrome.
- Animals, Chlorocebus aethiops, Dose-Response Relationship, Drug, Down-Regulation, Time Factors.
Abstract
Interferons (IFNs) inhibit severe acute respiratory syndrome coronavirus (SARS-CoV) replication and might be valuable for SARS treatment. In this study, we demonstrate that treatment of Vero E6 cells with interleukin-4 (IL-4) decreased the susceptibility of these cells to SARS-CoV infection. In contrast to IFNs, IL-4 did not show antiviral activity when administered immediately after SARS-CoV infection, suggesting that IL-4 acts early during the SARS-CoV replication cycle. Indeed, binding of recombinant SARS-CoV spike protein to Vero E6 cells was diminished on cells treated with IL-4, but also on cells exposed to IFN-gamma. Consistent with these observations, IL-4 and IFN-gamma downregulated cell surface expression of angiotensin-converting enzyme 2 (ACE2), the SARS-CoV receptor. Besides diminished ACE2 cell surface expression, ACE2 mRNA levels were also decreased after treatment with these cytokines. These findings suggest that IL-4 and IFN-gamma inhibit SARS-CoV replication partly through downregulation of ACE2.
DOI: 10.1016/j.virol.2006.06.011
PubMed: 16860835
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pubmed:16860835Le document en format XML
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<term>Down-Regulation</term>
<term>Interferon-gamma (pharmacology)</term>
<term>Interleukin-4 (pharmacology)</term>
<term>Receptors, Virus (drug effects)</term>
<term>Receptors, Virus (metabolism)</term>
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<term>Cellules Vero (métabolisme)</term>
<term>Facteurs temps</term>
<term>Interféron gamma (pharmacologie)</term>
<term>Interleukine-4 (pharmacologie)</term>
<term>Relation dose-effet des médicaments</term>
<term>Récepteurs viraux ()</term>
<term>Récepteurs viraux (métabolisme)</term>
<term>Régulation négative</term>
<term>Réplication virale ()</term>
<term>Syndrome respiratoire aigu sévère (virologie)</term>
<term>Virus du SRAS (physiologie)</term>
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<term>Interleukin-4</term>
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<term>Virus Replication</term>
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<term>Down-Regulation</term>
<term>Time Factors</term>
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<term>Cellules Vero</term>
<term>Facteurs temps</term>
<term>Relation dose-effet des médicaments</term>
<term>Récepteurs viraux</term>
<term>Régulation négative</term>
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<front><div type="abstract" xml:lang="en">Interferons (IFNs) inhibit severe acute respiratory syndrome coronavirus (SARS-CoV) replication and might be valuable for SARS treatment. In this study, we demonstrate that treatment of Vero E6 cells with interleukin-4 (IL-4) decreased the susceptibility of these cells to SARS-CoV infection. In contrast to IFNs, IL-4 did not show antiviral activity when administered immediately after SARS-CoV infection, suggesting that IL-4 acts early during the SARS-CoV replication cycle. Indeed, binding of recombinant SARS-CoV spike protein to Vero E6 cells was diminished on cells treated with IL-4, but also on cells exposed to IFN-gamma. Consistent with these observations, IL-4 and IFN-gamma downregulated cell surface expression of angiotensin-converting enzyme 2 (ACE2), the SARS-CoV receptor. Besides diminished ACE2 cell surface expression, ACE2 mRNA levels were also decreased after treatment with these cytokines. These findings suggest that IL-4 and IFN-gamma inhibit SARS-CoV replication partly through downregulation of ACE2.</div>
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