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Title: Tumor necrosis factor. alpha. functions in an autocrine manner in the induction of human immunodeficiency virus expression

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America; (USA)

Tumor necrosis factor {alpha} (TNF-{alpha}) is an immunoregulatory cytokine capable of inducing viral expression in cells chronically infected with the human immunodeficiency virus (HIV), such as the promonocytic line U1 and the T-lymphocytic line ACH-2. In the present study, the authors demonstrate an autocrine mechanism of TNF-{alpha}-mediated HIV induction. Stimulation of U1 and ACH-2 cells with phorbol 12-myristate 13-acetate (PMA) resulted in the induction of TNF-{alpha} mRNA and the secretion of TNF-{alpha}. Of note is the fact that anti-TNF-{alpha} antibodies significantly suppressed the expression of HIV in PMA-stimulated U1 and ACH-2 cells. Furthermore, anti-TNF-{alpha} antibodies also suppressed both the constitutive and inducible levels of viral expression in the chronically infected promonocytic clone U33.3. This study illustrates the interrelationship between the regulation of HIV expression and normal immunoregulatory mechanisms in that virus expression, both constitutive and induced, can be modulated by an autocrine pathway involving TNF-{alpha}, a cytokine involved in the complex network of regulation of the normal human immune response.

OSTI ID:
7064311
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 87:2; ISSN 0027-8424
Country of Publication:
United States
Language:
English