| |  Online-Ressource |
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| Verfasst von: | Urban, Christian [VerfasserIn]  |
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| | Welsch, Hendrik [VerfasserIn] |
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| | Heine, Katharina [VerfasserIn] |
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| | Wüst, Sandra [VerfasserIn] |
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| | Haas, Darya A. [VerfasserIn] |
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| | Dächert, Christopher [VerfasserIn] |
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| | Pandey, Aparna [VerfasserIn] |
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| | Pichlmair, Andreas [VerfasserIn] |
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| | Binder, Marco [VerfasserIn] |
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| Titel: | Persistent innate immune stimulation results in IRF3-mediated but caspase-independent cytostasis |
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| Verf.angabe: | Christian Urban, Hendrik Welsch, Katharina Heine, Sandra Wüst, Darya A. Haas, Christopher Dächert, Aparna Pandey, Andreas Pichlmair and Marco Binder |
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| E-Jahr: | 2020 |
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| Jahr: | 11 June 2020 |
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| Fussnoten: | Gesehen am 02.09.2020 |
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| Titel Quelle: | Enthalten in: Viruses |
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| Ort Quelle: | Basel : MDPI, 2009 |
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| Jahr Quelle: | 2020 |
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| Band/Heft Quelle: | 12(2020,6) Artikel-Nummer 635, 21 Seiten |
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| ISSN Quelle: | 1999-4915 |
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| Abstract: | Persistent virus infection continuously produces non-self nucleic acids that activate cell-intrinsic immune responses. However, the antiviral defense evolved as a transient, acute phase response and the effects of persistently ongoing stimulation onto cellular homeostasis are not well understood. To study the consequences of long-term innate immune activation, we expressed the NS5B polymerase of Hepatitis C virus (HCV), which in absence of viral genomes continuously produces immune-stimulatory RNAs. Surprisingly, within 3 weeks, NS5B expression declined and the innate immune response ceased. Proteomics and functional analyses indicated a reduced proliferation of those cells most strongly stimulated, which was independent of interferon signaling but required mitochondrial antiviral signaling protein (MAVS) and interferon regulatory factor 3 (IRF3). Depletion of MAVS or IRF3, or overexpression of the MAVS-inactivating HCV NS3/4A protease not only blocked interferon responses but also restored cell growth in NS5B expressing cells. However, pan-caspase inhibition could not rescue the NS5B-induced cytostasis. Our results underline an active counter selection of cells with prolonged innate immune activation, which likely constitutes a cellular strategy to prevent persistent virus infections. |
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| DOI: | doi:10.3390/v12060635 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: https://doi.org/10.3390/v12060635 |
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| | Volltext: https://www.mdpi.com/1999-4915/12/6/635 |
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| | DOI: https://doi.org/10.3390/v12060635 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | cytostasis |
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| | HCV |
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| | innate immunity |
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| | interferon |
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| | IRF3 |
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| | MAVS |
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| | RIG-I |
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| K10plus-PPN: | 1728623286 |
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| Verknüpfungen: | → Zeitschrift |
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Persistent innate immune stimulation results in IRF3-mediated but caspase-independent cytostasis / Urban, Christian [VerfasserIn]; 11 June 2020 (Online-Ressource)
