Activation of monocyte cyclooxygenase-2 gene expression by human herpesvirus 6. Role for cyclic AMP-responsive element-binding protein and activator protein-1.
Prostaglandin E(2) (PGE(2)) is an arachidonic acid metabolite mainly produced by activated monocytes/macrophages (Mo/Mphi) that display broad immunomodulatory activities. Several viruses capable of infecting Mo/Mphi modulate PGE(2) synthesis in a way that favors the infection processes and the spread of virions. In the present work, we studied the effect of human herpesvirus 6 (HHV-6) infection of Mo/Mphi on PGE(2) synthesis. Our results indicate that HHV-6 induces COX-2 gene expression and PGE(2) synthesis within a few hours of infection. We mapped the different promoter elements associated with COX-2 gene activation by HHV-6 to two cis-acting elements: a cyclic AMP-responsive element and an activator protein-1 element. HHV-6 immediate-early protein 2 was identified as a modulator of COX-2 gene expression in Mo/Mphi. Finally, addition of PGE(2) to HHV-6-infected peripheral blood mononuclear cells cultures was found to increase significantly viral replication. Overall, these results further contribute to the immunomodulatory properties of HHV-6 and highlight a potential role for eicosanoids in the replication process of this virus.
Janelle
Marie-Eve
ME
Laboratory of Virology and Laboratory of Viral Immunology, Rheumatology, and Immunology Research Center, CHUL Research Center and Faculty of Medicine, Laval University, Quebec G1V 4G2, Canada.
Gravel
Annie
A
Gosselin
Jean
J
Tremblay
Michel J
MJ
Flamand
Louis
L
D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology*; D051546:Cyclooxygenase 2; D004268:DNA-Binding Proteins / Q000502:physiology; D015232:Dinoprostone / Q000096:biosynthesis* / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D015654:Herpesvirus 6, Human / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008565:Membrane Proteins; D009000:Monocytes / Q000378:metabolism; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology; D015533:Transcriptional Activation; D014779:Virus Replication
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone