Induction of indoleamine 2,3-dioxygenase in primary human macrophages by HIV-1.
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.
School of Physiology and Pharmacology, Faculty of Medicine, University of New South Wales, Sydney, Australia.
R S
RS
Grant
H
H
Naif
S J
SJ
Thuruthyil
N
N
Nasr
T
T
Littlejohn
O
O
Takikawa
V
V
Kapoor
D001921:Brain / Q000821:virology; D002478:Cells, Cultured; D004790:Enzyme Induction; D018023:HIV Seronegativity; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma / Q000494:pharmacology; D007700:Kinetics; D007737:Kynurenine / Q000097:blood; D008264:Macrophages / Q000201:enzymology* / Q000821:virology*; D009000:Monocytes / Q000166:cytology; D014366:Tryptophan Oxygenase / Q000096:biosynthesis* / Q000097:blood
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D007371:Interferon-gamma; D014366:Tryptophan Oxygenase