Home LiteratureArticle Details
PMID: 12414962 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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

Journal of virology ·Vol. 76 ·No. 23 ·2002-12-00 ·Pages 12233-41

Burudi EM, Marcondes MC, Watry DD, Zandonatti M, Taffe MA, Fox HS

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-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.

MeSH Terms
AIDS Dementia Complex/etiology Animals Base Sequence Brain/enzymology,immunology,pathology Disease Models, Animal Gene Expression Regulation, Enzymologic Humans In Vitro Techniques Indoleamine-Pyrrole 2,3,-Dioxygenase Interferon-gamma/genetics,metabolism,pharmacology Macaca mulatta Mice Microglia/drug effects,enzymology Molecular Sequence Data RNA, Messenger/genetics,metabolism Recombinant Proteins Simian Acquired Immunodeficiency Syndrome/enzymology,genetics,immunology,pathology Tryptophan Oxygenase/genetics Tumor Necrosis Factor-alpha/metabolism
Chemicals
Indoleamine-Pyrrole 2,3,-Dioxygenase RNA, Messenger Recombinant Proteins Tumor Necrosis Factor-alpha Interferon-gamma Tryptophan Oxygenase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Burudi E M E
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA.
Marcondes M Cecilia G
Watry Debbie D
Zandonatti Michelle
Taffe Michael A
Fox Howard S
References (43)
43 references, click to expand
  1. Localization of simian immunodeficiency virus in the central nervous system of rhesus monkeys.
    Am J Pathol. 1991 Sep;139(3):609-21 PMID: 1716047
  2. Neocortical damage during HIV infection.
    Ann Neurol. 1991 Jun;29(6):651-7 PMID: 1909852
  3. Cognitive and motor impairments associated with SIV infection in rhesus monkeys.
    Science. 1992 Mar 6;255(5049):1246-9 PMID: 1546323
  4. Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease.
    Brain. 1992 Oct;115 ( Pt 5):1249-73 PMID: 1422788
  5. Intracerebral cytokine messenger RNA expression in acquired immunodeficiency syndrome dementia.
    Ann Neurol. 1993 Jun;33(6):576-82 PMID: 8498837
  6. Cytopathologic and neurochemical correlates of progression to motor/cognitive impairment in SIV-infected rhesus monkeys.
    J Neuropathol Exp Neurol. 1994 Mar;53(2):165-75 PMID: 8120538
  7. Seminars in medicine of the Beth Israel Hospital, Boston. Dementia associated with the acquired immunodeficiency syndrome.
    N Engl J Med. 1995 Apr 6;332(14):934-40 PMID: 7877652
  8. Transfer of neuropathogenic simian immunodeficiency virus with naturally infected microglia.
    Am J Pathol. 1995 Apr;146(4):914-23 PMID: 7717458
  9. Simian immunodeficiency virus (SIV)-specific CTL in cerebrospinal fluid and brains of SIV-infected rhesus macaques.
    J Immunol. 1995 May 15;154(10):5582-9 PMID: 7730657
  10. Frontal cortex indoleamine-2,3-dioxygenase activity is increased in HIV-1-associated dementia.
    Neurosci Lett. 1995 Feb 24;187(1):9-12 PMID: 7617307
  11. Increased human immunodeficiency virus (HIV) type 1 DNA content and quinolinic acid concentration in brain tissues from patients with HIV encephalopathy.
    J Infect Dis. 1995 Sep;172(3):638-47 PMID: 7658054
  12. Immunocytochemical quantitation of human immunodeficiency virus in the brain: correlations with dementia.
    Ann Neurol. 1995 Nov;38(5):755-62 PMID: 7486867
  13. Selective activation-induced apoptosis of peripheral T cells imposed by macrophages. A potential mechanism of antigen-specific peripheral lymphocyte deletion.
    J Immunol. 1996 Jan 15;156(2):523-32 PMID: 8543802
  14. Anti-parasitic effector mechanisms in human brain tumor cells: role of interferon-gamma and tumor necrosis factor-alpha.
    Eur J Immunol. 1996 Feb;26(2):487-92 PMID: 8617321
  15. Tumor necrosis factor-alpha production induced by viruses and by lipopolysaccharides in macrophages: similarities and differences.
    J Inflamm. 1995-1996;46(1):1-12 PMID: 8832967
  16. Expression of inflammatory cytokines and inducible nitric oxide synthase in brains of SIV-infected rhesus monkeys: applications to HIV-induced central nervous system disease.
    Mol Med. 1996 Jan;2(1):27-37 PMID: 8900532
  17. Chemokine expression in simian immunodeficiency virus-induced AIDS encephalitis.
    Am J Pathol. 1996 Nov;149(5):1459-67 PMID: 8909235
  18. Quinolinic acid and lymphocyte subsets in the intrathecal compartment as biomarkers of SIV infection and simian AIDS.
    AIDS Res Hum Retroviruses. 1997 Jul 1;13(10):891-7 PMID: 9197383
  19. Different kynurenine pathway enzymes limit quinolinic acid formation by various human cell types.
    Biochem J. 1997 Sep 1;326 ( Pt 2):351-6 PMID: 9291104
  20. Dendritic injury is a pathological substrate for human immunodeficiency virus-related cognitive disorders. HNRC Group. The HIV Neurobehavioral Research Center.
    Ann Neurol. 1997 Dec;42(6):963-72 PMID: 9403489
  21. Sources of the neurotoxin quinolinic acid in the brain of HIV-1-infected patients and retrovirus-infected macaques.
    FASEB J. 1998 Jul;12(10):881-96 PMID: 9657528
  22. Prevention of allogeneic fetal rejection by tryptophan catabolism.
    Science. 1998 Aug 21;281(5380):1191-3 PMID: 9712583
  23. Protective role of the virus-specific immune response for development of severe neurologic signs in simian immunodeficiency virus-infected macaques.
    J Virol. 1998 Dec;72(12):9940-7 PMID: 9811731
  24. Increased peroxynitrite activity in AIDS dementia complex: implications for the neuropathogenesis of HIV-1 infection.
    J Immunol. 1999 Apr 1;162(7):4319-27 PMID: 10201964
  25. A nonhuman primate model for the selective elimination of CD8+ lymphocytes using a mouse-human chimeric monoclonal antibody.
    Am J Pathol. 1999 Jun;154(6):1923-32 PMID: 10362819
  26. Viral load and neuropathology in the SIV model.
    J Neurovirol. 1999 Jun;5(3):232-40 PMID: 10414513
  27. Regulation of the kynurenine metabolic pathway by interferon-gamma in murine cloned macrophages and microglial cells.
    J Neurochem. 1996 Mar;66(3):996-1004 PMID: 8769859
  28. Induction of indolamine 2,3-dioxygenase in primary human macrophages by human immunodeficiency virus type 1 is strain dependent.
    J Virol. 2000 May;74(9):4110-5 PMID: 10756023
  29. Mitochondrial ATP synthase 6 as an endogenous control in the quantitative RT-PCR analysis of clinical cancer samples.
    Mol Diagn. 2000 Mar;5(1):39-46 PMID: 10837088
  30. Antiviral treatment normalizes neurophysiological but not movement abnormalities in simian immunodeficiency virus-infected monkeys.
    J Clin Invest. 2000 Jul;106(1):37-45 PMID: 10880046
  31. Cytokine mediated regulation of interferon-gamma-induced IDO activation.
    Adv Exp Med Biol. 1999;467:533-9 PMID: 10721097
  32. Indoleamine 2,3-dioxygenase production by human dendritic cells results in the inhibition of T cell proliferation.
    J Immunol. 2000 Apr 1;164(7):3596-9 PMID: 10725715
  33. Comparative quantification of IL-1beta, IL-10, IL-10r, TNFalpha and IL-7 mRNA levels in UV-irradiated human skin in vivo.
    Inflamm Res. 2000 Jun;49(6):290-6 PMID: 10939619
  34. Sensitive and robust one-tube real-time reverse transcriptase-polymerase chain reaction to quantify SIV RNA load: comparison of one- versus two-enzyme systems.
    AIDS Res Hum Retroviruses. 2000 Sep 1;16(13):1247-57 PMID: 10957722
  35. Elevated cerebrospinal fluid quinolinic acid levels are associated with region-specific cerebral volume loss in HIV infection.
    Brain. 2001 May;124(Pt 5):1033-42 PMID: 11335705
  36. Human primary CD4 + T cells activated in the presence of IFN-alpha 2b express functional indoleamine 2,3-dioxygenase.
    J Interferon Cytokine Res. 2001 Jun;21(6):431-7 PMID: 11440641
  37. Interferon-gamma-induced tryptophan degradation: neuropsychiatric and immunological consequences.
    Curr Drug Metab. 2000 Sep;1(2):193-204 PMID: 11465083
  38. Lipopolysaccharide induction of indoleamine 2,3-dioxygenase is mediated dominantly by an IFN-gamma-independent mechanism.
    Eur J Immunol. 2001 Aug;31(8):2313-8 PMID: 11477543
  39. Quinolinic acid is produced by macrophages stimulated by platelet activating factor, Nef and Tat.
    J Neurovirol. 2001 Feb;7(1):56-60 PMID: 11519483
  40. Central nervous system perivascular cells are immunoregulatory cells that connect the CNS with the peripheral immune system.
    Glia. 2001 Nov;36(2):156-64 PMID: 11596124
  41. Highly activated CD8(+) T cells in the brain correlate with early central nervous system dysfunction in simian immunodeficiency virus infection.
    J Immunol. 2001 Nov 1;167(9):5429-38 PMID: 11673562
  42. HIV in the brain: RNA levels and patterns of zidovudine resistance.
    Neurology. 2001 Oct 23;57(8):1396-401 PMID: 11673579
  43. Morphology and distribution of HIV-1 gp41-positive microglia in subacute AIDS encephalitis. Pattern of involvement resembling a multisystem degeneration.
    Acta Neuropathol. 1990;80(4):393-400 PMID: 2239151
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/jvi.76.23.12233-12241.2002
Published
2002-12-00
Pages
12233-41
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC136861
Subset
IM
Grants
NIMH NIH HHS · R01 MH061692-02 · United States
NIMH NIH HHS · R01 MH061692 · United States
NIMH NIH HHS · MH61692 · United States
NIMH NIH HHS · P30 MH062261 · United States
NIMH NIH HHS · R01 MH061692-01A2 · United States
NIMH NIH HHS · R01 MH059468 · United States
NIMH NIH HHS · MH61224 · United States
NIMH NIH HHS · MH59468 · United States
NCRR NIH HHS · RR13150 · United States
NIMH NIH HHS · MH62261 · United States
Databases
GENBANK
AF533656
External Links
PubMed source DOI: 10.1128/jvi.76.23.12233-12241.2002 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2