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.
Institute of Molecular Virology (IMV), Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms-University Muenster, Von-Esmarch-Str. 56, D-48149 Muenster, Germany.|Institute of Molecular Virology (IMV), Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms-University Muenster, Von-Esmarch-Str. 56, D-48149 Muenster, Germany.
Sabine Eva
SE
Dudek
Institute of Molecular Virology (IMV), Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms-University Muenster, Von-Esmarch-Str. 56, D-48149 Muenster, Germany.|Institute of Molecular Virology (IMV), Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms-University Muenster, Von-Esmarch-Str. 56, D-48149 Muenster, Germany.
Katja
K
Nitzsche
Institute of Molecular Virology (IMV), Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms-University Muenster, Von-Esmarch-Str. 56, D-48149 Muenster, Germany.|Institute of Molecular Virology (IMV), Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms-University Muenster, Von-Esmarch-Str. 56, D-48149 Muenster, Germany.|Cluster of Excellence Cells in Motion, University of Muenster, Muenster, Germany.
Stephan
S
Ludwig
Institute of Molecular Virology (IMV), Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms-University Muenster, Von-Esmarch-Str. 56, D-48149 Muenster, Germany.|Cluster of Excellence Cells in Motion, University of Muenster, Muenster, Germany.
Christina
C
Ehrhardt
D000072283:A549 Cells; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000071457:DEAD Box Protein 58 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D006207:Half-Life; D054884:Host-Pathogen Interactions; D006801:Humans; D009980:Influenza A virus / Q000502:physiology*; D007251:Influenza, Human / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D020871:RNA Stability; D012333:RNA, Messenger / Q000737:chemistry*; D012367:RNA, Viral / Q000235:genetics; D011971:Receptors, Immunologic; D051816:Tristetraprolin / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
D012333:RNA, Messenger; D012367:RNA, Viral; D011971:Receptors, Immunologic; D051816:Tristetraprolin; C497552:ZFP36 protein, human; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58