Induction of indoleamine 2,3-dioxygenase in primary human macrophages by HIV-1

Redox Rep. 2000;5(2-3):105-7. doi: 10.1179/135100000101535366.


Increased kynurenine pathway metabolism has been implicated in the aetiology of the AIDS dementia complex (ADC). The rate limiting enzyme for this pathway is indoleamine 2,3-dioxygenase (IDO). We tested the efficacy of different strains of HIV-1 (HIV1-BaL, HIV1-JRFL and HIV1-631) to induce IDO in cultured human monocyte-derived macrophages (MDM). A significant increase in both IDO protein and kynurenine synthesis was observed after 48 h in MDM infected with the brain derived HIV-1 isolates, laboratory adapted (LA) HIV1-JRFL, and primary isolate HIV1-631. In contrast, almost no kynurenine production or IDO protein was evident in MDM infected with the high replicating macrophage tropic LA strain, HIV1-BaL. The induction of IDO and kynurenine synthesis by HIV1-JRFL and HIV1-631 declined to baseline levels by day-8 post-infection. Together, these results indicate that only selected strains of HIV-1 are capable of inducing IDO synthesis and subsequent oxidative tryptophan catabolism in MDM.

MeSH terms

  • Brain / virology
  • Cells, Cultured
  • Enzyme Induction
  • HIV Seronegativity
  • HIV-1 / physiology*
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Interferon-gamma / pharmacology
  • Kinetics
  • Kynurenine / blood
  • Macrophages / enzymology*
  • Macrophages / virology*
  • Monocytes / cytology
  • Tryptophan Oxygenase / biosynthesis*
  • Tryptophan Oxygenase / blood


  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Kynurenine
  • Interferon-gamma
  • Tryptophan Oxygenase