HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Culver, C. A. Articles by Laster, S. M. Search for Related Content PubMed PubMed Citation Articles by Culver, C. A. Articles by Laster, S. M.

Adenovirus Type 5 Exerts Multiple Effects on the Expression and Activity of Cytosolic Phospholipase A₂, Cyclooxygenase-2, and Prostaglandin Synthesis¹

Department of Microbiology, North Carolina State University, Raleigh, NC 27695

In this study, we examine how infection of murine and human fibroblasts by adenovirus (Ad) serotype 5 (Ad5) affects the expression and activity of cytosolic phospholipase A₂ (cPLA₂), cyclooxygenase-2 (COX-2), and production of PGs. Our experiments showed that infection with Ad5 is accompanied by the rapid activation of cPLA₂ and the cPLA₂-dependent release of [³H]arachidonic acid ([³H]AA). Increased expression of COX-2 was also observed after Ad infection, as was production of PGE₂ and PGI₂. Later, however, as the infection progressed, release of [³H]AA and production of PGs stopped. Late-stage Ad5-infected cells also did not release [³H]AA or PGs following treatment with a panel of biologically diverse agents. Experiments with UV-inactivated virus confirmed that Ad infection is accompanied by the activation of a host-dependent response that is later inhibited by the virus. Investigations of the mechanism of suppression of the PG pathway by Ad5 did not reveal major effects on the expression or activity of cPLA₂ or COX-2. We did note a change in the intracellular position of cPLA₂ and found that cPLA₂ did not translocate normally in infected cells, raising the possibility that Ad5 interferes with the PG pathway by interfering with the intracellular movement of cPLA₂. Taken together, these data reveal dynamic interactions between Ad5 and the lipid mediator pathways of the host and highlight a novel mechanism by which Ad5 evades the host immune response. In addition, our results offer insight into the inflammatory response induced by many Ad vectors lacking early region gene products.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Grant CA59032 from the National Institutes of Health (to S.M.L.), Project 06333 from the North Carolina Agricultural Research Service (to S.M.L.), and George Hitchings New Investigator Award from the Burroughs Wellcome Fund (to C.A.C.).

² Address correspondence and reprint requests to Dr. Scott M. Laster, Department of Microbiology, North Carolina State University, Raleigh, NC 27695-7615. E-mail address: scott_laster{at}ncsu.edu

³ Abbreviations used in this paper: PLA₂, phospholipase A₂; AA, arachidonic acid; Ad, adenovirus; Ad5, Ad serotype 5; COX, cyclooxygenase; cPLA₂, cytosolic PLA₂; p.i., postinfection.