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J. Biol. Chem., Vol. 277, Issue 34, 30665-30674, August 23, 2002
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From the Prostaglandin E2
(PGE2) is an arachidonic acid metabolite mainly produced by
activated monocytes/macrophages (Mo/M
Activation of Monocyte Cyclooxygenase-2 Gene Expression by Human
Herpesvirus 6
ROLE FOR CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN AND
ACTIVATOR PROTEIN-1*
,,
**, and
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 and Laboratory of
Human Immuno-Retrovirology, Research Center in Infectious Diseases,
CHUL Research Center and Faculty of Medicine, Laval University, Quebec
G1V 4G2, Canada
) that display broad
immunomodulatory activities. Several viruses capable of infecting
Mo/M modulate PGE2 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/M
on PGE2 synthesis. Our results indicate that HHV-6 induces COX-2 gene expression and PGE2 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/M. Finally,
addition of PGE2 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.
*
This work was supported in part by Canadian Institutes for
Health Research Grants HOP-14437 and MOP 36048 (to L. F.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Canadian Institutes for Health Research young investigator
awardee. To whom correspondence should be addressed: Rheumatology and
Immunology Research Center, Local T1-49, 2705 Blvd. Laurier, Sainte-Foy, Quebec, Canada, G1V 4G2. Tel.: 418-654-2772; Fax: 418-654-2765; E-mail: Louis.Flamand@crchul.ulaval.ca.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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