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Journal of Virology, December 2002, p. 12233-12241, Vol. 76, No. 23
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.23.12233-12241.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Regulation of Indoleamine 2,3-Dioxygenase Expression in Simian Immunodeficiency Virus-Infected Monkey Brains{dagger}

E. M. E. Burudi, M. Cecilia G. Marcondes, Debbie D. Watry, Michelle Zandonatti, Michael A. Taffe, and Howard S. Fox*

Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037

Received 4 April 2002/ Accepted 23 August 2002

The human immunodeficiency virus type 1-associated cognitive-motor disorder, including the AIDS dementia complex, is characterized by brain functional abnormalities that are associated with injury initiated by viral infection of the brain. Indoleamine 2,3-dioxygenase (IDO), the first and rate-limiting enzyme in tryptophan catabolism in extrahepatic tissues, can lead to neurotoxicity through the generation of quinolinic acid and immunosuppression and can alter brain chemistry via depletion of tryptophan. Using the simian immunodeficiency virus (SIV)-infected rhesus macaque model of AIDS, we demonstrate that cells of the macrophage lineage are the main source for expression of IDO in the SIV-infected monkey brain. Animals with SIV encephalitis have the highest levels of IDO mRNA, and the level of IDO correlates with gamma interferon (IFN-{gamma}) and viral load levels. In vitro studies on mouse microglia reveal that IFN-{gamma} is the primary inducer of IDO expression. These findings demonstrate the link between IDO expression, IFN-{gamma} levels, and brain pathology signs observed in neuro-AIDS.

* Corresponding author. Mailing address: Department of Neuropharmacology, CVN 8, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 784-7171. Fax: (858) 784-7296. E-mail: hsfox{at}scripps.edu.

{dagger} Paper 14882-NP from The Scripps Research Institute.

Journal of Virology, December 2002, p. 12233-12241, Vol. 76, No. 23
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.23.12233-12241.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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