Tumor necrosis factor antagonizes inhibitory effect of azidothymidine on human immunodeficiency virus (HIV) replication in vitro

Biochem Biophys Res Commun. 1990 Feb 14;166(3):1095-101. doi: 10.1016/0006-291x(90)90979-w.

Abstract

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.

MeSH terms

  • Biotransformation
  • Cell Line
  • Cell Survival / drug effects
  • Chromatography, High Pressure Liquid
  • Dextran Sulfate
  • Dextrans / pharmacology
  • Dose-Response Relationship, Drug
  • HIV-1 / drug effects
  • HIV-1 / physiology*
  • Humans
  • Nucleotides / isolation & purification
  • Recombinant Proteins / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Virus Replication / drug effects*
  • Zalcitabine / pharmacology
  • Zidovudine / antagonists & inhibitors
  • Zidovudine / metabolism
  • Zidovudine / pharmacology*

Substances

  • Dextrans
  • Nucleotides
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Zidovudine
  • Zalcitabine
  • Dextran Sulfate