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Journal of Virology, May 2000, p. 4110-4115, Vol. 74, No. 9
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Induction of Indolamine 2,3-Dioxygenase in Primary Human Macrophages by Human Immunodeficiency Virus Type 1 Is Strain Dependent

Ross S. Grant,1 Hassan Naif,2,* Sophie J. Thuruthyil,1 Najla Nasr,2 Tamantha Littlejohn,3 Osamu Takikawa,3 and Vimal Kapoor1,*

School of Physiology and Pharmacology, Faculty of Medicine, University of New South Wales, Sydney 2052,1 Centre for Virus Research, University of Sydney, Westmead Hospital, Westmead 2145,2 and Australian Cataract Research Foundation, University of Wollongong, Wollongong 2522,3 New South Wales, Australia

Received 7 June 1999/Accepted 28 January 2000

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-gamma ) to induce IDO and kynurenine synthesis in HIV-infected MDM. The addition of anti-IFN-gamma 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-gamma in MDM responding to the initial infection with selected strains of HIV-1.

* Corresponding author. Mailing address for V. Kapoor: School of Physiology and Pharmacology, Faculty of Medicine, University of New South Wales, Sydney 2052, Australia. Phone: 61-2 93853741. Fax: 61-2 93851099. E-mail: V.Kapoor{at}unsw.edu.au. Mailing address for H. Naif: Centre for Virus Research, University of Sydney, Westmead Hospital, Westmead 2145, Australia. Phone: 61-2 98456311. Fax: 61-2 98458300. E-mail: hassann{at}westgate.wh.usyd.edu.au.

Journal of Virology, May 2000, p. 4110-4115, Vol. 74, No. 9
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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