Prevention of Activation of HIV-1 by Antiviral Agents in OM-10.1 Cells

Abstract

The development of a reliable and simple system for evaluating compounds that could prevent activation of latent HIV would allow us to devise new therapeutic approaches. These compounds could eventually be used in combination with drugs that are effective against acute and chronic infections. The OM-10.1 cell line is a chronically infected clone which remains CD4+ until HIV-1 activation with tumour necrosis factor-α. A variety of compounds are known to have antiviral properties against either acutely or chronically infected cells were evaluated for their ability to inhibit HIV induced expression in these cells. We also examined the effect of several compounds that interact with biochemical pathways that may interfere with or enhance the reactivation process. These included nucleoside analogues, cytokines, steroidal and nonsteroidal anti-inflammatory agents, polyoxometalates, a TAT inhibitor, various natural products (including nerve growth factor, N-acetyl-L-cysteine, taxol, and interferons), TIBO, porphyrins, and various oligomers. CD4 cellular expression and supernatant reverse transcriptase activity were quantitated as markers of induced viral expression. Among the 58 compounds evaluated, 3′-fluoro-3′-deoxythymidine (FLT), interferon γ, Ro 5–3335 (a TAT inhibitor) and desferrioxamine were modest and selective inhibitors of HIV-1 activation.