EBV suppresses prostaglandin E-2 biosynthesis in human monocytes

It is well known that EBV has developed strategies to evade immune surveill ance. Previously, EBV was shown to bind specifically to monocytes and regul ate expression of proinflammatory mediators such as IL-1, IL-6, TNF-alpha, and leukotrienes, EBV was also found to affect phagocytosis of monocytes, T n this study, we show that in addition to these effects, EBV suppresses the biosynthesis of PGE,, a pleiotropic immunomodulatory molecule that is synt hesized by the dioxygenation of arachidonic acid via the cyclooxygenase (CO X) pathway, This down-regulation of PGE, formation involved the inhibition of the inducible COX-2 isoform expression both at the transcriptional and t ranslational levels, whereas expression of the constitutive COX-1 isoform w as unaltered. Furthermore, exposure of monocytes to EBV was found to impact on the NF-KB activation pathway, which plays an essential role in the Indu ction of COX-2 in monocytes, The inhibition of PGE, biosynthesis was reliev ed when the experiments were conducted in presence of phosphonoacetic acid, an inhibitor of herpesviruses DNA polymerase, indicating that viral replic ation and/or neosynthesized viral proteins were involved in this process. T hus, inhibition of PGE, biosynthesis in monocytes may represent an addition al mechanism underlying EBV pathogenicity.