ATP1A1-mediated Src signaling inhibits coronavirus entry into host cells.
Identifieur interne : 001912 ( Main/Curation ); précédent : 001911; suivant : 001913ATP1A1-mediated Src signaling inhibits coronavirus entry into host cells.
Auteurs : Christine Burkard [Pays-Bas] ; Monique H. Verheije [Pays-Bas] ; Bart L. Haagmans [Pays-Bas] ; Frank J. Van Kuppeveld [Pays-Bas] ; Peter J M. Rottier [Pays-Bas] ; Berend-Jan Bosch [Pays-Bas] ; Cornelis A M. De Haan [Pays-Bas]Source :
- Journal of virology [ 1098-5514 ] ; 2015.
Descripteurs français
- KwdFr :
- Animaux, Attachement viral (), Bufanolide (pharmacologie), Cellules Vero, Concentration en ions d'hydrogène, Coronavirus félin (physiologie), Extinction de l'expression des gènes, Glucosides cardiotoniques (pharmacologie), Humains, Infections à Coronaviridae (physiopathologie), Lignée cellulaire, Ouabaïne (pharmacologie), Petit ARN interférent (génétique), Pénétration virale (), Réaction de polymérisation en chaine en temps réel, Sodium-Potassium-Exchanging ATPase (métabolisme), Souris, Transduction du signal (physiologie), Virus de l'hépatite murine (physiologie).
- MESH :
- génétique : Petit ARN interférent.
- métabolisme : Sodium-Potassium-Exchanging ATPase.
- pharmacologie : Bufanolide, Glucosides cardiotoniques, Ouabaïne.
- physiologie : Coronavirus félin, Transduction du signal, Virus de l'hépatite murine.
- physiopathologie : Infections à Coronaviridae.
- Animaux, Attachement viral, Cellules Vero, Concentration en ions d'hydrogène, Extinction de l'expression des gènes, Humains, Lignée cellulaire, Pénétration virale, Réaction de polymérisation en chaine en temps réel, Souris.
English descriptors
- KwdEn :
- Animals, Bufanolides (pharmacology), Cardiac Glycosides (pharmacology), Cell Line, Chlorocebus aethiops, Coronaviridae Infections (physiopathology), Coronavirus, Feline (physiology), Gene Silencing, Humans, Hydrogen-Ion Concentration, Mice, Murine hepatitis virus (physiology), Ouabain (pharmacology), RNA, Small Interfering (genetics), Real-Time Polymerase Chain Reaction, Signal Transduction (physiology), Sodium-Potassium-Exchanging ATPase (metabolism), Vero Cells, Virus Attachment (drug effects), Virus Internalization (drug effects).
- MESH :
- chemical , genetics : RNA, Small Interfering.
- chemical , metabolism : Sodium-Potassium-Exchanging ATPase.
- chemical , pharmacology : Bufanolides, Cardiac Glycosides, Ouabain.
- drug effects : Virus Attachment, Virus Internalization.
- physiology : Coronavirus, Feline, Murine hepatitis virus, Signal Transduction.
- physiopathology : Coronaviridae Infections.
- Animals, Cell Line, Chlorocebus aethiops, Gene Silencing, Humans, Hydrogen-Ion Concentration, Mice, Real-Time Polymerase Chain Reaction, Vero Cells.
Abstract
In addition to transporting ions, the multisubunit Na(+),K(+)-ATPase also functions by relaying cardiotonic steroid (CTS)-binding-induced signals into cells. In this study, we analyzed the role of Na(+),K(+)-ATPase and, in particular, of its ATP1A1 α subunit during coronavirus (CoV) infection. As controls, the vesicular stomatitis virus (VSV) and influenza A virus (IAV) were included. Using gene silencing, the ATP1A1 protein was shown to be critical for infection of cells with murine hepatitis virus (MHV), feline infectious peritonitis virus (FIPV), and VSV but not with IAV. Lack of ATP1A1 did not affect virus binding to host cells but resulted in inhibited entry of MHV and VSV. Consistently, nanomolar concentrations of the cardiotonic steroids ouabain and bufalin, which are known not to affect the transport function of Na(+),K(+)-ATPase, inhibited infection of cells with MHV, FIPV, Middle East respiratory syndrome (MERS)-CoV, and VSV, but not IAV, when the compounds were present during virus inoculation. Cardiotonic steroids were shown to inhibit entry of MHV at an early stage, resulting in accumulation of virions close to the cell surface and, as a consequence, in reduced fusion. In agreement with an early block in infection, the inhibition of VSV by CTSs could be bypassed by low-pH shock. Viral RNA replication was not affected when these compounds were added after virus entry. The antiviral effect of ouabain could be relieved by the addition of different Src kinase inhibitors, indicating that Src signaling mediated via ATP1A1 plays a crucial role in the inhibition of CoV and VSV infections.
DOI: 10.1128/JVI.03274-14
PubMed: 25653449
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pubmed:25653449Le document en format XML
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<term>Chlorocebus aethiops</term>
<term>Coronaviridae Infections (physiopathology)</term>
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<term>RNA, Small Interfering (genetics)</term>
<term>Real-Time Polymerase Chain Reaction</term>
<term>Signal Transduction (physiology)</term>
<term>Sodium-Potassium-Exchanging ATPase (metabolism)</term>
<term>Vero Cells</term>
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<term>Virus Internalization (drug effects)</term>
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<term>Attachement viral ()</term>
<term>Bufanolide (pharmacologie)</term>
<term>Cellules Vero</term>
<term>Concentration en ions d'hydrogène</term>
<term>Coronavirus félin (physiologie)</term>
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<term>Glucosides cardiotoniques (pharmacologie)</term>
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<term>Infections à Coronaviridae (physiopathologie)</term>
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<term>Réaction de polymérisation en chaine en temps réel</term>
<term>Sodium-Potassium-Exchanging ATPase (métabolisme)</term>
<term>Souris</term>
<term>Transduction du signal (physiologie)</term>
<term>Virus de l'hépatite murine (physiologie)</term>
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<front><div type="abstract" xml:lang="en">In addition to transporting ions, the multisubunit Na(+),K(+)-ATPase also functions by relaying cardiotonic steroid (CTS)-binding-induced signals into cells. In this study, we analyzed the role of Na(+),K(+)-ATPase and, in particular, of its ATP1A1 α subunit during coronavirus (CoV) infection. As controls, the vesicular stomatitis virus (VSV) and influenza A virus (IAV) were included. Using gene silencing, the ATP1A1 protein was shown to be critical for infection of cells with murine hepatitis virus (MHV), feline infectious peritonitis virus (FIPV), and VSV but not with IAV. Lack of ATP1A1 did not affect virus binding to host cells but resulted in inhibited entry of MHV and VSV. Consistently, nanomolar concentrations of the cardiotonic steroids ouabain and bufalin, which are known not to affect the transport function of Na(+),K(+)-ATPase, inhibited infection of cells with MHV, FIPV, Middle East respiratory syndrome (MERS)-CoV, and VSV, but not IAV, when the compounds were present during virus inoculation. Cardiotonic steroids were shown to inhibit entry of MHV at an early stage, resulting in accumulation of virions close to the cell surface and, as a consequence, in reduced fusion. In agreement with an early block in infection, the inhibition of VSV by CTSs could be bypassed by low-pH shock. Viral RNA replication was not affected when these compounds were added after virus entry. The antiviral effect of ouabain could be relieved by the addition of different Src kinase inhibitors, indicating that Src signaling mediated via ATP1A1 plays a crucial role in the inhibition of CoV and VSV infections.</div>
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