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Influenza A viruses suppress cyclooxygenase-2 expression by affecting its mRNA stability

Infection with influenza A viruses (IAV) provokes activation of cellular defence mechanisms contributing to the innate immune and inflammatory response. In this process the cyclooxygenase-2 (COX-2) plays an important role in the induction of prostaglandin-dependent inflammation. While it has been reported that COX-2 is induced upon IAV infection, in the present study we observed a down-regulation at later stages of infection suggesting a tight regulation of COX-2 by IAV. Our data indicate the pattern-recognition receptor RIG-I as mediator of the initial IAV-induced COX-2 synthesis. Nonetheless, during on-going IAV replication substantial suppression of COX-2 mRNA and protein synthesis could be detected, accompanied by a decrease in mRNA half-life. Interestingly, COX-2 mRNA stability was not only imbalanced by IAV replication but also by stimulation of cells with viral RNA. Our results reveal tristetraprolin (TTP), which is known to bind COX-2 mRNA and promote its rapid degradation, as regulator of COX-2 expression in IAV infection. During IAV replication and viral RNA accumulation TTP mRNA synthesis was induced, resulting in reduced COX-2 levels. Accordingly, the down-regulation of TTP resulted in increased COX-2 protein expression after IAV infection. These findings indicate a novel IAV-regulated cellular mechanism, contributing to the repression of host defence and therefore facilitating viral replication.

Titel: Influenza A viruses suppress cyclooxygenase-2 expression by affecting its mRNA stability
Verfasser: Dudek, Sabine Eva GND
Nitzsche, Katja GND
Ludwig, Stephan
Ehrhardt, Christina GND
Organisation: FB 13: Biologie
Dokumenttyp: Artikel
Medientyp: Text
Erscheinungsdatum: 06.06.2016
Publikation in MIAMI: 22.09.2016
Datum der letzten Änderung: 16.04.2019
Quelle: Scientific Reports 6 (2016) 27275, 1-13
Fachgebiete: Medizin und Gesundheit
Lizenz: CC BY 4.0
Sprache: Englisch
Anmerkungen: Finanziert durch den Open-Access-Publikationsfonds 2015/2016 der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format: PDF-Dokument
URN: urn:nbn:de:hbz:6-64269522380
DOI: 10.1038/srep27275
ISSN: 2045-2322