OxyFile #218

Activation of the HIV long terminal repeat and viral production 
by H2O2-vanadate.

Author:   Kazazi F; Koehler JK; Klebanoff SJ;

Source:   Free Radic Biol Med 1996; 20(6):813-20


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 (H2O2). 
We report here that H2O2-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 H2O2. H2O2 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 H2O2 and 
vanadate concentrations down to 3 x 10(-6) M, with high 
concentrations leading to cell toxicity. Catalase was strongly 
inhibitory when added prior to the interaction of H2O2 
and vanadate, but was considerably less inhibitory when 
the H2O2 and vanadate were allowed to preincubate prior 
to the catalase addition. H2O2 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.