Activation of monocyte cyclooxygenase-2 gene expression by human herpesvirus 6. Role for cyclic AMP-responsive element-binding protein and activator protein-1

J Biol Chem. 2002 Aug 23;277(34):30665-74. doi: 10.1074/jbc.M203041200. Epub 2002 Jun 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Cyclic AMP Response Element-Binding Protein / physiology*
  • Cyclooxygenase 2
  • DNA-Binding Proteins / physiology
  • Dinoprostone / biosynthesis*
  • Dinoprostone / pharmacology
  • Gene Expression Regulation, Enzymologic*
  • Herpesvirus 6, Human / drug effects
  • Herpesvirus 6, Human / physiology*
  • Humans
  • Isoenzymes / genetics*
  • Membrane Proteins
  • Monocytes / metabolism
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Promoter Regions, Genetic
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • T-Lymphocytes / immunology
  • Transcription Factor AP-1 / physiology*
  • Transcription Factors / physiology
  • Transcriptional Activation
  • Virus Replication


  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • Isoenzymes
  • Membrane Proteins
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Transcription Factor AP-1
  • Transcription Factors
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone