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.


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@article{Grant2000InductionOI, title={Induction of indoleamine 2,3-dioxygenase in primary human macrophages by HIV-1.}, author={Ross Grant and Hassan M. Naif and Sophy J Thuruthyil and Najla Nasr and Tamantha K Littlejohn and Osamu Takikawa and Vishal Kapoor}, journal={Redox report : communications in free radical research}, year={2000}, volume={5 2-3}, pages={105-7} }