N-ACETYL-L-CYSTEINE-INDUCED UP-REGULATION OF HIV-1 GENE-EXPRESSION INMONOCYTE-DERIVED MACROPHAGES CORRELATES WITH INCREASED NF-KAPPA-B DNA-BINDING ACTIVITY

Nuclear factor kappa B (NF-kappa B) is an important cellular regulator of human immunodeficiency virus (HIV) gene expression, In T cells, N- acetyl-L-cysteine (NAC) inhibits the induction of NF-kappa B and trans cription of HIV-1. However, NAC up-regulates HIV-1 replication in mono cyte-derived macrophages (MDM). In this study we demonstrate that NAC treatment of MDM transfected with a chloramphenicol acetyltransferase (CAT) construct under transcriptional control of the HIV-1 long termin al repeat resulted in an up-regulation of CAT activity. Furthermore, M DM transfected with a HIV-1-NF-kappa B-CAT construct also produced inc reased CAT activity after NAC treatment, In addition, electrophoretic mobility shift assays revealed that nuclei of NAG-treated MDM containe d increased binding activity to wild-type, but not mutant, ICE oligonu cleotides. Components of the binding activity were identified with ant ibodies as the NF-kappa B subunits p50 and p65, These data indicate th at NAG-induced enhancement of HIV-1 replication in MDM is regulated at the level of viral gene expression and mediated by NF-kappa B.