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Updated: Sep 30, 2026

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Activation of monocyte cyclooxygenase-2 gene expression by human herpesvirus 6. Role for cyclic AMP-responsive
Marie-Eve Janelle1, Annie Gravel, Jean Gosselin
1Laboratory 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.
Abstract:
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.
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