Regulation of indoleamine 2,3-dioxygenase expression in simian immunodeficiency virus-infected monkey brains

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

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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-γ) and viral load levels. In vitro studies on mouse microglia reveal that IFN-γ is the primary inducer of IDO expression. These findings demonstrate the link between IDO expression, IFN-γ levels, and brain pathology signs observed in neuro-AIDS.

Original languageEnglish (US)
Pages (from-to)12233-12241
Number of pages9
JournalJournal of virology
Volume76
Issue number23
DOIs
StatePublished - Dec 1 2002

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Indoleamine-Pyrrole 2,3,-Dioxygenase
Simian immunodeficiency virus
Simian Immunodeficiency Virus
Haplorhini
monkeys
brain
Brain
interferons
Tryptophan
tryptophan
Interferons
Brain Chemistry
Acquired Immunodeficiency Syndrome
AIDS Dementia Complex
Quinolinic Acid
neurotoxicity
dementia
immunosuppression
neuroglia
Microglia

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Regulation of indoleamine 2,3-dioxygenase expression in simian immunodeficiency virus-infected monkey brains. / Burudi, E. M.E.; Marcondes, M. Cecilia G.; Watry, Debbie D.; Zandonatti, Michelle; Taffe, Michael A.; Fox, Howard S.

In: Journal of virology, Vol. 76, No. 23, 01.12.2002, p. 12233-12241.

Research output: Contribution to journalArticle

Burudi, E. M.E. ; Marcondes, M. Cecilia G. ; Watry, Debbie D. ; Zandonatti, Michelle ; Taffe, Michael A. ; Fox, Howard S. / Regulation of indoleamine 2,3-dioxygenase expression in simian immunodeficiency virus-infected monkey brains. In: Journal of virology. 2002 ; Vol. 76, No. 23. pp. 12233-12241.
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