Tumor necrosis factor. alpha. and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor. kappa. B

Journal Article · Sat Apr 01 04:00:00 EST 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.7.2336· OSTI ID:5228507

Osborn, L; Kunkel, S; Nabel, G J ^[1]

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1. Howard Hughes Medical Institute, Ann Arbor, MI (USA)

Binding of peptide hormones to surface membrane receptors leads to the transcription of specific genes within relevant target cells. How these signals are transduced to alter gene expression is largely unknown, but this mechanism probably involves a sequence of enzymatic steps that activate factors in the nucleus that modulate transcription. The authors demonstrate that two different peptide hormones, or cytokines, stimulate the human immunodeficiency virus enhancer, and this effect is mediated by nuclear factor (NF) {kappa}B. These cytokines, tumor necrosis factor {alpha} and interleukin 1, act on multiple cell types and represent the only naturally occurring activators of this transcription factor among eight cytokines examined. Although NF-{kappa}B binding can be stimulated by phorbol 12-myristate 13-acetate, tumor necrosis factor {alpha} acts through an independent mechanism, inducing NF-{kappa}B binding in HT-2 cells, which did not show increased binding in response to phorbol 12-myristate 13-acetate, and causing superinduction in Jurkat T-lymphoma cells. These findings suggest that human immunodeficiency virus gene expression can be induced in T cells without activating lymphokine secretion and that the role of these cytokines in the activation of latent human immunodeficiency virus infection deserves further clinical evaluation. Finally, this link between binding at the surface membrane and stimulation of a specific transcription factor should help define intermediates for these cytokine activation pathways.

• OSTI ID: 5228507
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 86:7; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
AIDS VIRUS
ANIMAL CELLS
BIOCHEMISTRY
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARCINOGENS
CELL PROLIFERATION
CHEMICAL ACTIVATION
CHEMISTRY
CONNECTIVE TISSUE CELLS
ELECTROPHORESIS
ENZYME ACTIVITY
ESTERS
GENES
GROWTH FACTORS
HORMONES
LEUKOCYTES
LYMPHOCYTES
LYMPHOKINES
MATERIALS
MEMBRANE PROTEINS
MEMBRANES
MICROORGANISMS
MITOGENS
NECROSIS
ORGANIC COMPOUNDS
PARASITES
PATHOLOGICAL CHANGES
PEPTIDE HORMONES
PHORBOL ESTERS
PROTEINS
SOMATIC CELLS
TRANSCRIPTION
TUMOR CELLS
VIRUSES