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 replication, 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 increased 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 radicals play an important role in self-sustained HIV-1 replication in macrophages and that oxygen radical scavengers other than NAC should be considered as therapeutic agents for AIDS patients.
Nottet
H S
HS
Eijkman-Winkler Laboratory for Medical Microbiology, University of Utrecht, The Netherlands.
van Asbeck
B S
BS
de Graaf
L
L
de Vos
N M
NM
Visser
M R
MR
Verhoef
J
J
D000111:Acetylcysteine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D005296:Ferrous Compounds / Q000378:metabolism; D016166:Free Radical Scavengers; D005978:Glutathione / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013268:Stimulation, Chemical; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014508:Urea / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects* / Q000502:physiology*
D005296:Ferrous Compounds; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; C038983:1,3-dimethylthiourea; D014508:Urea; D005978:Glutathione; D013890:Thiourea; D000111:Acetylcysteine