Presenter: Carolyn A.
Advisor(s): Dr. Scott Laster
Author(s): Carolyn A. Culver, Susan M. Michalowski, Scott Laster
Graduate Program: Microbiology
Title: Adenovirus Infection Inhibits the Production of PGE2
Abstract: In this report we examine the effects of adenovirus (Ad) infection on the production of PGE2. Our experiments show complete inhibition of PGE2 production by infection with Ad 5. PGE2 production was blocked in both murine and human cell types following stimulation with a variety of ligands including LPS, A23187, and PMA. Surprisingly, the expression of COX-1 or COX-2 was not blocked by infection with Ad 5; in fact Ad 5 infection strongly induced expression of COX-2 protein. Moving upstream we examined the effects of Ad on cPLA2 expression and activity. We found that release of 3H-arachidonic acid was completely blocked by Ad infection. This effect was seen with both Ad 2 and Ad 5 and occurred with E3 deletion mutants indicating that this is a novel, non-E3 encoded activity. Again we did not find an effect on the expression of cPLA2 or its activity in cell lysates. Agonist induced phosphorylation of cPLA2 serine 505 was also not affected. In an effort to understand this phenomenon we examined the intracellular position of cPLA2. We found that infection with Ad causes cPLA2 to shift from its normal cytosolic location to the nuclear region of the cell. Both perinuclear and intranuclear staining were noted. Subsequently, following agonist stimulation, the cPLA2 in Ad infected cells did not translocate as it does normally. We conclude therefore that Ad inhibits production of PGE2 by causing the intracellular relocation of cPLA2 to a position that prevents its participation in inflammatory responses. (Supported by NIH grant CA59032, NCARS project 06333, and the Hitchings New Investigator Award from the Burroughs Wellcome Fund.