Blood, Vol. 93 No. 1 (January 1), 1999:
pp. 350-356
Activation of the Human Immunodeficiency Virus-1 Long Terminal
Repeat by Respiratory Burst Oxidants of Neutrophils
Seymour J. Klebanoff and
Catherine M. Headley
From the Department of Medicine, University of Washington, Seattle.
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.
