Tumor necrosis factor alpha induces expression of human immunodeficiency virus in a chronically infected T-cell clone.
Tumor necrosis factor alpha (TNF-alpha), also known as cachectin, was demonstrated to induce the expression of human immunodeficiency virus (HIV) in a chronically infected T-cell clone (ACH-2). Concentrations of recombinant TNF-alpha as low as 50 pg/ml induced a significant increase over background of HIV expression in the ACH-2 cells as determined by supernatant reverse transcriptase activity. The HIV-inducing effects of TNF-alpha could not be explained by toxic effects on the cells. In addition, both the uninfected parental cell line (A3.01) and the infected ACH-2 cells were shown to have high-affinity receptors for TNF-alpha. Transient-transfection experiments demonstrated that the inductive effects of TNF-alpha were due to specific activation of the HIV long terminal repeat. These studies provide evidence that TNF-alpha may play a role in the mechanisms of pathogenesis of HIV infection.
Folks
T M
TM
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Clouse
K A
KA
Justement
J
J
Rabson
A
A
Duh
E
E
Kehrl
J H
JH
Fauci
A S
AS
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells; D005786:Gene Expression Regulation / Q000187:drug effects; D005814:Genes, Viral / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D006801:Humans; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha