Activation of the human immunodeficiency virus-1 long terminal repeat by respiratory burst oxidants of neutrophils.
The human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) introduced in association with the luciferase reporter gene into Jurkat T cells was strongly activated by a combination of human neutrophils and phorbol myristate acetate (PMA). Activation was not observed when normal neutrophils were replaced by neutrophils which lack a respiratory burst, ie, from a patient with chronic granulomatous disease (CGD), was strongly inhibited by catalase, was potentiated by vanadate, was stimulated by relatively low concentrations of azide, and was inhibited by selective inhibitors of protein kinase C (PKC). The PMA affected activation in three ways: (1) by directly activating the LTR in Jurkat LTRluc; (2) by inducing a respiratory burst in neutrophils with the formation of H2O2; and (3) by increasing the sensitivity of Jurkat LTRluc to the activating effect of H2O2. When PMA was replaced by opsonized zymosan as the neutrophil stimulus, activation of the LTR was low unless azide was added. Activation in the presence of azide was not seen when CGD neutrophils were used or when catalase was added, suggesting that azide acts by inhibiting the degradation of H2O2. These findings indicate that activation of the HIV-1 LTR in Jurkat T cells can be induced by H2O2 released by neutrophils, particularly when PKC is concomitantly activated.
Klebanoff
S J
SJ
Department of Medicine, University of Washington, Seattle 98195-7185, USA. seym@u.washington.edu
Headley
C M
CM
D005786:Gene Expression Regulation / Q000187:drug effects; D016325:HIV Long Terminal Repeat / Q000187:drug effects; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D019169:Jurkat Cells; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D016877:Oxidants / Q000502:physiology*; D016897:Respiratory Burst / Q000187:drug effects / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014638:Vanadates / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D016877:Oxidants; D014638:Vanadates; D015054:Zymosan; D006861:Hydrogen Peroxide; D013755:Tetradecanoylphorbol Acetate