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Laboratories of
*
Viral Immunology and
Virology, Centre de recherche en Rhumatologie et Immunologie, and
Unit of Human ImmunoRetrovirology, Centre de recherche en Infectiologie, Centre de recherche du Centre Hospitalier de l’Université Laval, Université Laval, Québec, Canada
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-
, 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-
B 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.
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M.-E. Janelle, A. Gravel, J. Gosselin, M. J. Tremblay, and L. Flamand 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., August 16, 2002; 277(34): 30665 - 30674. [Abstract] [Full Text] [PDF]
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M. Tardif, M. Savard, L. Flamand, and J. Gosselin Impaired Protein Kinase C Activation/Translocation in Epstein-Barr Virus-infected Monocytes J. Biol. Chem., June 28, 2002; 277(27): 24148 - 24154. [Abstract] [Full Text] [PDF]
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S. Murono, H. Inoue, T. Tanabe, I. Joab, T. Yoshizaki, M. Furukawa, and J. S. Pagano Induction of cyclooxygenase-2 by Epstein-Barr virus latent membrane protein 1 is involved in vascular endothelial growth factor production in nasopharyngeal carcinoma cells PNAS, June 5, 2001; 98(12): 6905 - 6910. [Abstract] [Full Text] [PDF]
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