Tumor necrosis factor and interferon as prognostic markers in human immunodeficiency virus (HIV) infection

Infection ◽  
1991 ◽  
Vol 19 (S2) ◽  
pp. S93-S97 ◽  
Author(s):  
G. Hess ◽  
S. Rossol ◽  
R. Rossol ◽  
K. -H. Meyer zum Büschenfelde
Keyword(s):  
Human Immunodeficiency Virus ◽  
Tumor Necrosis Factor ◽  
Hiv Infection ◽  
Tumor Necrosis ◽  
Prognostic Markers ◽  
Immunodeficiency Virus ◽  
Necrosis Factor

scholarly journals Monocytes Treated with Human Immunodeficiency Virus Tat Kill Uninfected CD4+ Cells by a Tumor Necrosis Factor-Related Apoptosis-Induced Ligand-Mediated Mechanism

2003 ◽  
Vol 77 (12) ◽  
pp. 6700-6708 ◽  
Author(s):  
Yida Yang ◽  
Ilia Tikhonov ◽  
Tracy J. Ruckwardt ◽  
Mahmoud Djavani ◽  
Juan Carlos Zapata ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Cell Surface Expression ◽  
Monocyte Subset ◽  
Hiv Tat ◽  
Immunodeficiency Virus ◽  
Necrosis Factor

ABSTRACT The human immunodeficiency virus (HIV) Tat protein has a critical role in viral transcription, but this study focuses on its additional role as an extracellular effector of lymphocyte cell death. It is well known that Tat induces tumor necrosis factor-related apoptosis-induced ligand (TRAIL) in peripheral blood mononuclear cells (PBMC), and we show that the majority of TRAIL is produced by the monocyte subset of PBMC. Human monocytes and U937 monoblastoid cells did not take up soluble HIV Tat-86, as T cells did, yet produced more TRAIL than did T cells. TRAIL secretion was induced by Tat and by a cysteine-rich peptide of Tat but not by sulfhydryl-modified Tat toxoid. Although there was only a slight increase in cell surface expression of TRAIL on monocytes, sufficient TRAIL was secreted to be toxic for T cells. The cytotoxicity of Tat-stimulated monocyte medium could be blocked by a TRAIL-neutralizing antibody. T cells treated with Tat did not secrete enough TRAIL to mediate cell death in our assay. Remarkably, uninfected T cells are more susceptible to TRAIL than are HIV-infected T cells. The production of TRAIL by Tat-stimulated monocytes provides a mechanism by which HIV infection can destroy uninfected bystander cells.

Alteration of tumor necrosis factor–α T-cell homeostasis following potent antiretroviral therapy: contribution to the development of human immunodeficiency virus–associated lipodystrophy syndrome

Blood ◽  
2000 ◽  
Vol 95 (10) ◽  
pp. 3191-3198 ◽  
Author(s):  
Eric Ledru ◽  
Névéna Christeff ◽  
Olivier Patey ◽  
Pierre de Truchis ◽  
Jean-Claude Melchior ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Interleukin 2 ◽  
Hiv Patients ◽  
Immunodeficiency Virus ◽  
Necrosis Factor

Abstract Highly-active antiretroviral therapy (HAART) has lead to a dramatic decrease in the morbidity of patients infected with the human immunodeficiency virus (HIV). However, metabolic side effects, including lipodystrophy-associated (LD-associated) dyslipidemia, have been reported in patients treated with antiretroviral therapy. This study was designed to determine whether successful HAART was responsible for a dysregulation in the homeostasis of tumor necrosis factor- (TNF-), a cytokine involved in lipid metabolism. Cytokine production was assessed at the single cell level by flow cytometry after a short-term stimulation of peripheral blood T cells from HIV-infected (HIV+) patients who were followed during 18 months of HAART. A dramatic polarization to TNF- synthesis of both CD4 and CD8 T cells was observed in all patients. Because it was previously shown that TNF- synthesis by T cells was highly controlled by apoptosis, concomitant synthesis of TNF- and priming for apoptosis were also analyzed. The accumulation of T cells primed for TNF- synthesis is related to their escape from activation-induced apoptosis, partly due to the cosynthesis of interleukin-2 (IL-2) and TNF-. Interestingly, we observed that LD is associated with a more dramatic TNF- dysregulation, and positive correlations were found between the absolute number of TNF- CD8 T-cell precursors and lipid parameters usually altered in LD including cholesterol, triglycerides, and the atherogenic ratio apolipoprotein B (apoB)/apoA1. Observations from the study indicate that HAART dysregulates homeostasis of TNF- synthesis and suggest that this proinflammatory response induced by efficient antiretroviral therapy is a risk factor of LD development in HIV+ patients.

scholarly journals A proliferative p53-responsive element mediates tumor necrosis factor alpha induction of the human immunodeficiency virus type 1 long terminal repeat.

1995 ◽  
Vol 15 (6) ◽  
pp. 3450-3459 ◽  
Author(s):  
A Gualberto ◽  
M L Hixon ◽  
T S Finco ◽  
N D Perkins ◽  
G J Nabel ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Tumor Necrosis Factor ◽  
Long Terminal Repeat ◽  
Binding Sites ◽  
Tumor Necrosis ◽  
Terminal Repeat ◽  
Mutant P53 ◽  
Immunodeficiency Virus ◽  
Necrosis Factor

Transforming mutants of the p53 tumor suppressor gene can positively regulate transcription from several promoters that do not contain known p53 binding sites. Here, we report the identification of a novel p53 binding site in the human immunodeficiency virus long terminal repeat that specifically mediates mutant p53 transactivation. This DNA element was bound by endogenous Jurkat p53 when these cells were stimulated by tumor necrosis factor. Mutation of this sequence inhibited p53 transactivation and tumor necrosis factor inducibility of the human immunodeficiency virus type 1 long terminal repeat. In addition, this DNA element was found to be sufficient to confer mutant p53 responsiveness on a heterologous minimal promoter. It has been hypothesized that transforming mutants of p53 represent a proliferative conformational stage that can be adopted by the native protein under stimulation by growth factors. The data presented suggest that proliferative and antiproliferative p53 conformations recognize different DNA binding sites in order to mediate distinct biological functions. Thus, transforming mutants of p53 that fold into the proliferative conformation would favor proliferative over antiproliferative functions.

scholarly journals Tumor necrosis factor-dependent production of human immunodeficiency virus 1 in chronically infected HL-60 cells

Blood ◽  
1993 ◽  
Vol 82 (9) ◽  
pp. 2742-2748 ◽  
Author(s):  
K Kitano ◽  
CI Rivas ◽  
GC Baldwin ◽  
JC Vera ◽  
DW Golde
Keyword(s):  
Human Immunodeficiency Virus ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Virus Production ◽  
Viral Production ◽  
Low Concentrations ◽  
Immunodeficiency Virus ◽  
Lag Period ◽  
Low Levels ◽  
Necrosis Factor

Abstract Tumor necrosis factor (TNF) may play a central role in proviral activation and release from latency in cells infected with the human immunodeficiency virus (HIV). We studied viral production and its relation to TNF in a HL-60 cell line (J22-HL-60) infected with a monocytotropic strain of HIV-1JR-FL. Viral production was stimulated to similar levels by TNF, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), and 1,25-dihydroxyvitamin D3 (1,25[OH]2D3). Production of the virus was not suppressed by 3′-azido-3′-deoxythymidine (AZT), indicating that viral production was not caused by superinfection. Low concentrations of TNF (0.1 ng/mL) induced viral production with a short lag period of 8 hours, and this proviral activation was specifically suppressed by anti- TNF antibodies. However, induction of virus production by 1,25(OH)2D3 showed an extended lag period of 2 to 3 days. The effect of 1,25(OH)2D3 on virus production was also blocked by anti-TNF antibodies, which suggests the direct participation of TNF in this process. TNF accumulated in the culture supernatant of cells stimulated with 1,25(OH)2D3 with a kinetics consistent with its involvement in the action of 1,25(OH)2D3 on viral production. The J22-HL-60 cell line produced low levels of virus when cultured in the absence of an external stimulus; however, this basal viral production was suppressed greater than 80% in the presence of anti-TNF antibodies. Corresponding low levels of TNF were detected in the culture supernatants. Viral production decreased slowly with increasing passage of the cells, and no virus was detected in the supernatants of cells maintained in culture for several months. Concomitantly, TNF was no longer detected in the supernatant of these cells, which suggests that endogenous autocrine production of TNF drives viral production in the unstimulated cells. However, viral production was stimulated in these cells by low concentrations (0.1 ng/mL) of added TNF. These results argue for a central role for TNF in HIV proviral activation in chronically infected myeloid cells.

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