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Induction of indolamine 2,3-dioxygenase in primary human macrophages by human immunodeficiency virus type 1 is strain dependent

Journal Article


Abstract


  • Increased kynurenine pathway metabolism has been implicated in the etiology of AIDS dementia complex (ADC). The rate-limiting enzyme for this pathway is indolamine 2,3-dioxygenase (IDO). We tested the efficacy of different strains of human immunodeficiency virus type 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 highly 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 postinfection. Abundant HIV-1 replication did not reduce the ability of exogenous gamma interferon (IFN-γ) to induce IDO and kynurenine synthesis in HIV-infected MDM. The addition of anti-IFN-γ antibody to MDM infected with HIV1-JRFL resulted in an absence of detectable IDO protein after 48 h and a decrease of 64% ± 1% in supernatant kynurenine concentration. Together, these results indicate that only selected strains of HIV-1 are capable of inducing IDO synthesis and subsequent kynurenine metabolism in MDM. The induction of IDO, while apparently independent of replication capacity, appears to be mediated by a transient production of IFN-γ in MDM responding to the initial infection with selected strains of HIV-1.

Publication Date


  • 2000

Citation


  • Grant, R. S., Naif, H., Thuruthyil, S. J., Nasr, N., Littlejohn, T., Takikawa, O., & Kapoor, V. (2000). Induction of indolamine 2,3-dioxygenase in primary human macrophages by human immunodeficiency virus type 1 is strain dependent. Journal of Virology, 74(9), 4110-4115. doi:10.1128/JVI.74.9.4110-4115.2000

Scopus Eid


  • 2-s2.0-0033998033

Start Page


  • 4110

End Page


  • 4115

Volume


  • 74

Issue


  • 9

Abstract


  • Increased kynurenine pathway metabolism has been implicated in the etiology of AIDS dementia complex (ADC). The rate-limiting enzyme for this pathway is indolamine 2,3-dioxygenase (IDO). We tested the efficacy of different strains of human immunodeficiency virus type 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 highly 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 postinfection. Abundant HIV-1 replication did not reduce the ability of exogenous gamma interferon (IFN-γ) to induce IDO and kynurenine synthesis in HIV-infected MDM. The addition of anti-IFN-γ antibody to MDM infected with HIV1-JRFL resulted in an absence of detectable IDO protein after 48 h and a decrease of 64% ± 1% in supernatant kynurenine concentration. Together, these results indicate that only selected strains of HIV-1 are capable of inducing IDO synthesis and subsequent kynurenine metabolism in MDM. The induction of IDO, while apparently independent of replication capacity, appears to be mediated by a transient production of IFN-γ in MDM responding to the initial infection with selected strains of HIV-1.

Publication Date


  • 2000

Citation


  • Grant, R. S., Naif, H., Thuruthyil, S. J., Nasr, N., Littlejohn, T., Takikawa, O., & Kapoor, V. (2000). Induction of indolamine 2,3-dioxygenase in primary human macrophages by human immunodeficiency virus type 1 is strain dependent. Journal of Virology, 74(9), 4110-4115. doi:10.1128/JVI.74.9.4110-4115.2000

Scopus Eid


  • 2-s2.0-0033998033

Start Page


  • 4110

End Page


  • 4115

Volume


  • 74

Issue


  • 9