ROLE FOR OXYGEN RADICALS IN SELF-SUSTAINED HIV-1 REPLICATION IN MONOCYTE-DERIVED MACROPHAGES - ENHANCED HIV-1 REPLICATION BY N-ACETYL-L-CYSTEINE

N-acetyl-L-cysteine (NAG) has been proposed as a therapeutic agent for AIDS patients because it reduces human immunodeficiency virus type I (HIV-1) replication in stimulated T cells. However, NAC and glutathion e enhanced acute HIV-1 replication in monocyte-derived macrophages. Bu thionine sulfoximine did not affect NAG-mediated enhanced HIV-1 replic ation, indicating that the NAG-mediated effects are glutathione-indepe ndent. Superoxide dismutase and the hydroxyl radical scavengers dimeth ylthiourea and thiourea, but not urea, inhibited acute HIV-1 replicati on in macrophages. NAC reduced ferricytochrome c and increased dose-de pendently Fe(III)-citrate and Fe(III)EDTA-catalyzed hydroxyl radical f ormation in a system using glucose and glucose oxidase. Dimethylthiour ea and thiourea, but not urea and superoxide dismutase, dose-dependent ly inhibited NAG-mediated enhancement of HIV-1 replication. These data suggest that oxygen radicals play an important role in self-sustained HIV-1 replication in macrophages and that oxygen radical scavengers o ther than NAC should be considered as therapeutic agents for AIDS pati ents.