PMID- 12068008 OWN - NLM STAT- MEDLINE DCOM- 20020923 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 277 IP - 34 DP - 2002 Aug 23 TI - Activation of monocyte cyclooxygenase-2 gene expression by human herpesvirus 6. Role for cyclic AMP-responsive element-binding protein and activator protein-1. PG - 30665-74 AB - 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. FAU - Janelle, Marie-Eve AU - Janelle ME AD - 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. FAU - Gravel, Annie AU - Gravel A FAU - Gosselin, Jean AU - Gosselin J FAU - Tremblay, Michel J AU - Tremblay MJ FAU - Flamand, Louis AU - Flamand L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20020614 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (DNA-Binding Proteins) RN - 0 (Isoenzymes) RN - 0 (Membrane Proteins) RN - 0 (NFATC Transcription Factors) RN - 0 (Nuclear Proteins) RN - 0 (Transcription Factor AP-1) RN - 0 (Transcription Factors) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 1.14.99.1 (PTGS2 protein, human) RN - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - Cells, Cultured MH - Cyclic AMP Response Element-Binding Protein/*physiology MH - Cyclooxygenase 2 MH - DNA-Binding Proteins/physiology MH - Dinoprostone/*biosynthesis/pharmacology MH - *Gene Expression Regulation, Enzymologic MH - Herpesvirus 6, Human/drug effects/*physiology MH - Humans MH - Isoenzymes/*genetics MH - Membrane Proteins MH - Monocytes/metabolism MH - NFATC Transcription Factors MH - *Nuclear Proteins MH - Promoter Regions, Genetic MH - Prostaglandin-Endoperoxide Synthases/*genetics MH - T-Lymphocytes/immunology MH - Transcription Factor AP-1/*physiology MH - Transcription Factors/physiology MH - Transcriptional Activation MH - Virus Replication EDAT- 2002/06/18 10:00 MHDA- 2002/09/24 06:00 CRDT- 2002/06/18 10:00 PHST- 2002/06/18 10:00 [pubmed] PHST- 2002/09/24 06:00 [medline] PHST- 2002/06/18 10:00 [entrez] AID - S0021-9258(20)70144-4 [pii] AID - 10.1074/jbc.M203041200 [doi] PST - ppublish SO - J Biol Chem. 2002 Aug 23;277(34):30665-74. doi: 10.1074/jbc.M203041200. Epub 2002 Jun 14.