title: EBV suppresses prostaglandin E2 biosynthesis in human monocytes.
abstract: It is well known that EBV has developed strategies to evade immune surveillance. Previously, EBV was shown to bind specifically to monocytes and regulate expression of proinflammatory mediators such as IL-1, IL-6, TNF-alpha, and leukotrienes. EBV was also found to affect phagocytosis of monocytes. In this study, we show that in addition to these effects, EBV suppresses the biosynthesis of PGE2, a pleiotropic immunomodulatory molecule that is synthesized by the dioxygenation of arachidonic acid via the cyclooxygenase (COX) pathway. This down-regulation of PGE2 formation involved the inhibition of the inducible COX-2 isoform expression both at the transcriptional and translational levels, whereas expression of the constitutive COX-1 isoform was unaltered. Furthermore, exposure of monocytes to EBV was found to impact on the NF-kappaB activation pathway, which plays an essential role in the induction of COX-2 in monocytes. The inhibition of PGE2 biosynthesis was relieved when the experiments were conducted in presence of phosphonoacetic acid, an inhibitor of herpesviruses DNA polymerase, indicating that viral replication and/or neosynthesized viral proteins were involved in this process. Thus, inhibition of PGE2 biosynthesis in monocytes may represent an additional mechanism underlying EBV pathogenicity.
authors.affiliation: Laboratories of Viral Immunology, Hospitalier de l'Université Laval, Université Laval, Québec, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Savard
authors.forename: C
authors.initials: C
authors.lastname: Bélanger
authors.forename: M J
authors.initials: MJ
authors.lastname: Tremblay
authors.forename: N
authors.initials: N
authors.lastname: Dumais
authors.forename: L
authors.initials: L
authors.lastname: Flamand
authors.forename: P
authors.initials: P
authors.lastname: Borgeat
authors.forename: J
authors.initials: J
authors.lastname: Gosselin
mesh_terms: D001692:Biological Transport / Q000276:immunology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology; D008565:Membrane Proteins; D009000:Monocytes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000494:pharmacology; D014775:Virus Activation / Q000276:immunology
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D016328:NF-kappa B; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone