Tumor necrosis factor antagonizes inhibitory effect of azidothymidine on human immunodeficiency virus (HIV) replication in vitro.
Tumor necrosis factor alpha (TNF-alpha) completely reverses the activity of azidothymidine (AZT) against human immunodeficiency virus type 1 (HIV-1) in MOLT-4 cell cultures. The 50% effective concentration of AZT, required to protect MOLT-4 cells against the cytopathic effect of HIV-1, increased from 5.8 nM in the absence of TNF-alpha to greater than 125 microM in the presence of TNF-alpha (100 U/ml). TNF-alpha also antagonized the anti-HIV-1 activity of dideoxycytidine but did not markedly affect the anti-HIV-1 activity of dextran sulfate. The intracellular phosphorylation pattern of AZT was not changed upon the presence of TNF-alpha.
Ito
M
M
Department of Bacteriology, Fukushima Medical College, Japan.
Baba
M
M
Mori
S
S
Hirabayashi
K
K
Sato
A
A
Shigeta
S
S
De Clercq
E
E
D001711:Biotransformation; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D016264:Dextran Sulfate; D003911:Dextrans / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009711:Nucleotides / Q000302:isolation & purification; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*; D016047:Zalcitabine / Q000494:pharmacology; D015215:Zidovudine / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*
D003911:Dextrans; D009711:Nucleotides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D015215:Zidovudine; D016047:Zalcitabine; D016264:Dextran Sulfate