Activation of the HIV long terminal repeat and viral production by H 2O 2-vanadate

Abstract

The long terminal repeat (LTR) of human immunodeficiency virus type 1 (HIV-1) contains sequences required for the initiation of gene transcription. Among the substances known to activate the HIV-1 LTR is hydrogen peroxide (H202). We report here that H 2O 2-induced activation of the LTR in the macrophage cell line THP-1 and the lymphocyte cell line, Jurkat, is greatly increased by vanadate. Activation of the LTR by phorbol myristate acetate, tumor necrosis factor alpha, lipopolysaccharide, or Staphylococcus epidermidis extract was not increased by vanadate, indicating some selectivity for H 2O 2. H 2O 2 and vanadate also acted synergistically to increase the production of HIV-1 virions by the latently infected macrophage cell line U-1 as determined by p24 antigen release and the detection of intact virions by electron microscopy. Effects were observed at H 2O 2 and vanadate concentrations down to 3 × 10 −6, with high concentrations leading to cell toxicity. Catalase was strongly inhibitory when added prior to the interaction of H 2O 2 and vanadate, but was considerably less inhibitory when the H 2O 2 and vanadate were allowed to preincubate prior to the catalase addition. H 2O 2 reacts with vanadate to form peroxides of vanadate that have potent biological effects. Our findings suggest that among these is the activation of the HIV-1 LTR.