MODULATION OF THE ANTIVIRAL 2-5A SYSTEM IN HUMAN IMMUNODEFICIENCY VIRUS-1-INFECTED CEM CELLS BY PROPENTOFYLLINE

2',5'-Oligoadenylates (2-5A) play an essential role in the establishme nt of the antiviral state of cells exposed to virus infection. However , - after an initial increase observed in some cell lines - the activi ty of the interferon (IFN)-inducible, 2-5A-forming 2',5'-oligoadenylat e synthetase (2-5A synthetase) strongly decreases soon after infection of cells with the human immunodeficiency virus-1 (HIV-1). In the pres ent report, we show that in IFN-treated human T lymphoblastoid CEM cel ls, the decrease in 2-5A synthetase activity had already occurred at d ay 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 syn thetase activity was accompanied by a decrease in 2-5A synthetase mRNA and protein. We found that the decrease in 2-5A synthetase activity c an be retarded by addition of the cAMP phosphodiesterase inhibitor, pr opentofylline. At a concentration of 30-100 mu M, propentofylline disp layed a significant cytoprotective and antiviral effect on HIV-1-infec ted CEM cells.