%0 Article %A Dudek, Sabine Eva %A Nitzsche, Katja %A Ludwig, Stephan %A Ehrhardt, Christina %D 2016 %G English %@ 2045-2322 %T Influenza A viruses suppress cyclooxygenase-2 expression by affecting its mRNA stability %U https://nbn-resolving.de/urn:nbn:de:hbz:6-64269522380 %U https://repositorium.uni-muenster.de/document/miami/0eb2a20d-cdf0-43a5-b073-1b04b51757f8/srep27275.pdf %7 [Electronic ed.] %X 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.