OxyFile #216

HIV type 1 glycoprotein 120 amplifies tumor necrosis factor-
induced NF-kappa B activation in Jurkat cells.


Author: Shatrov VA; Ratter F; Gruber A; Dröge W; Lehmann V;

Source: AIDS Res Hum Retroviruses 1996 Sep 1; 12(13):1209-16

Abstract:

This article demonstrates that human immunodeficiency virus 
type 1 (HIV-1) gp120 amplifies the activity of tumor necrosis 
factor alpha (TNF-alpha), a cytokine that stimulates HIV-1 
replication through activation of NF-kappa B. In CD4-positive 
Jurkat cells, gp120 potentiates TNF-induced NF-kappa B 
activation. TNF-mediated activation of NF-kappa B is known 
to involve the intracellular formation of reactive oxygen 
intermediates (ROIs). Accordingly, we examined the influence 
of gp120 on the cellular redox state. We found that gp 
120-modulated TNF-induced NK-kappa B activation was inhibited 
by the antioxidant butylated hydroxyanisole, indicating 
the involvement of redox-dependent mechanisms. In addition, 
we showed that gp120 induces intracellular formation of 
hydrogen peroxide, which is accompanied by a decrease in 
the ratio of glutathione to glutathione disulfide. In contrast, 
in the p56lck-deficient J.CaM1.6 T cell line, a derivative 
of the Jurkat cell line, gp120 was unable to stimulate 
hydrogen peroxide, to decrease the ratio of GSH to GSSG, 
and has no effect on TNF-induced NF-kappa B activation. 
This demonstrated that p56lck protein tyrosine kinase plays 
an active role in transmitting a signal that increases 
the oxidative state of the cell and as a consequence amplifies 
TNF-mediated NF-kappa B DNA binding. We have demonstrated 
that Tat protein decreased both the Mn-dependent superoxide 
dismutase (MnSOD) and the cellular glutathione content 
(GSH). Here we show that, in contrast to Tat, gp120 is 
unable to inhibit activity and expression of MnSOD and 
to decrease GSH content. Taken together, our data suggest 
that gp120 potentiates TNF-induced NF-kappa B activation 
by stimulating a signal pathway that involves p56lck and 
the increased formation of reactive oxygen intermediates 
such as H2O2. These findings may be relevant for the regulation 
of HIV-1 replication in T cells.