Modulation of the Antiviral 2-5A System in Human Immunodeficiency Virus-1-Infected CEM Cells by Propentofylline

Abstract

2′,5′-OIigoadenylates (2-5A) play an essential role in the establishment of the antiviral state of cells exposed to virus infection. However, - after an initial increase observed in some cell lines - the activity of the interferon (IFN)-inducible, 2-5A-forming 2′,5′-oligoadenylate synthetase (2-5A synthetase) strongly decreases soon after infection of cells with the human immunodeficiency virus-1 (HIV-1). In the present report, we show that in IFN-treated human T lymphoblastoid CEM cells, the decrease in 2-5A synthetase activity had already occurred at day 1 post infection (p.i.)- At days 3 and 5 p.i., the 2-5A synthetase activity in the IFN-treated infected cells amounted to only 10-12% of that in IFN-treated uninfected control cells. The decrease in 2-5A synthetase activity was accompanied by a decrease in 2-5A synthetase mRNA and protein. We found that the decrease in 2-5A synthetase activity can be retarded by addition of the cAMP phosphodiesterase inhibitor, propentofylline. At a concentration of 30-100 μM, propentofylline displayed a significant cytoprotective and antiviral effect on HIV-1-infected CEM cells.