ALPHA-LIPOIC ACID BLOCKS HIV-1 LTR-DEPENDENT EXPRESSION OF HYGROMYCINRESISTANCE IN THP-1 STABLE TRANSFORMANTS

Gene expression of human immunodeficiency virus (HIV) depends on a hos t cellular transcription factors including nuclear factor-kappa B (NF- kappa B). The involvement of reactive oxygen intermediates (ROI) has b een implicated as intracellular messengers in the inducible activation of NF-kappa B, In this study, we compared the efficacy of two antioxi dants, alpha-lipoic acid (LA) and N-acetylcysteine (NAG), which are wi dely recognized NF-kappa B inhibitors, Here,we demonstrate that LA has a more potent activity in inhibiting NP-kappa B-mediated gene express ion in THP-1 cells that have been stably transfected with a plasmid be aring a hygromycin B resistance gene under the control of HIV-1 long t erminal repeat (LTR) promoter, The spontaneous activation of NF-kappa B in this cell culture system leads to expression of the hygromycin ph osphotransferase gene hence rendering the cells resistance to hygromyc in B. In this study, the effect of the test compounds against transcri ptional activity of HIV-1 LTR was evaluated based on the degree of cel lular toxicity due to the inhibitory activity on the expression of hyg romycin B resistance gene in the presence of hygromycin B, We also fou nd that 0.2 mM LA could cause 40% reduction in the HIV-1 expression fr om the TNF-alpha-stimulated OM 10.1, a cell line latently infected wit h HIV-1, On the other hand, 10 mM NAC was required to elicit the same effect. Furthermore, the initiation of HIV-1 induction by TNF-alpha wa s completely abolished by 1 mM LA, These findings confirm the involvem ent of ROI in NF-kappa B-mediated HIV gene expression as well as the e fficacy of LA as a therapeutic regimen for HIV infection and acquired immunodeficiency syndrome (AIDS), Moreover, this study validates the a pplicability of our present assay system which we primarily designed f or the screening of candidate drugs against HIV-1 gene expression.