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 (NAC) has been proposed as a therapeutic agent for AIDS patients because it reduces human immunodeficiency virus type 1 (HIV-1) replication in stimulated T cells. However, NAC and glutathione enhanced acute HIV-1 replication in monocyte-derived macrophages. Buthionine sulfoximine did not affect NAC-mediated enhanced HIV-1 replica- tion, indicating that the NAC-mediated effects are glutathione-independent. Superoxide dismutase and the hydroxyl radical scavengers dimethylthiourea and thiourea, but not urea, inhibited acute HIV-1 replication in macrophages. NAC reduced ferricytochrome c and in- creased dose-dependently Fe(III)-citrate and Fe(III)- EDTA-catalyzed hydroxyl radical formation in a system using glucose and glucose oxidase. Dimethylthiourea and thiourea, but not urea and superoxide dismutase, dose- dependently inhibited NAC-mediated enhancement of HIV-1 replication. These data suggest that oxygen radi- cals play an important role in self-sustained HIV-1 repli- cation in macrophages and that oxygen radical scavengers other than NAC should be considered as therapeutic agents for AIDS patients. J. Leukoc. Biol. 56: 702-707; 1994.