ACTIVATION OF THE HIV LONG TERMINAL REPEAT AND VIRAL PRODUCTION BY H2O2-VANADATE

The long terminal repeat (LTR) of human immunodeficiency virus type 1 (HIV-1) contains sequences required for the initiation of gene transcr iption. Among the substances known to activate the HN-I LTR is hydroge n peroxide (H2O2). We report here that H2O2-induced activation of the LTR in the macrophage cell line THP-1 and the lymphocyte cell line, Ju rkat, is greatly increased by vanadate. Activation of the LTR by phorb ol myristate acetate, tumor necrosis factor alpha, Lipopolysaccharide, or Staphylococcus epidermidis extract was not increased by vanadate, indicating some selectivity for H2O2. H2O2 and vanadate also acted syn ergistically to increase the production of HIV-1 virions by the latent ly infected macrophage cell line U-1 as determined by p24 antigen rele ase and the detection of intact virions by electron microscopy. Effect s were observed at H2O2 and vanadate concentrations down to 3 x 10(-6) M, with high concentrations leading to cell toxicity. Catalase was st rongly inhibitory when added prior to the interaction of H2O2 and vana date, but was considerably less inhibitory when the H2O2 and vanadate were allowed to preincubate prior to the catalase addition. H2O2 react s with vanadate to form peroxides of vanadate that have potent biologi cal effects. Our findings suggest that among these is the activation o f the HIV-1 LTR.