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 c ells was strongly activated by a combination of human neutrophils and phorb ol myristate acetate (PMA). Activation was not observed when normal neutrop hils 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 prote in kinase C (PKC). The PMA affected activation in three ways: (1) by direct ly activating the LTR in Jurkat LTRluc; (2) by inducing a respiratory burst in neutrophils with the formation of H2O2; and (3) by increasing the sensi tivity of Jurkat LTRluc to the activating effect of H2O2 When PMA was repla ced 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 indic ate that activation of the HIV-1 LTR in Jurkat T cells can be induced by H2 O2 released by neutrophils, particularly when PKC is concomitantly activate d. (C) 1999 by The American Society of Hematology.