An analysis of HIV-1-associated inflammatory products in brain tissue of humans and SCID mice with HIV-1 encephalitis

Yuri Persidsky, Manuel Buttini, Jenae Limoges, Paul Bock, Howard Eliot Gendelman

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

The human immunodeficiency virus type 1 (HIV)-associated dementia complex (ADC) is a neuroimmunological disorder fueled by viral replication in mononuclear phagocytes (MP) (brain macrophages and microglia). The elucidation of MP inflammatory factors involved in neurological dysfunction is pivotal for unraveling pathogenic mechanisms and in developing new therapies for this disease. Recent advances in animal model systems for ADC and its associated encephalitis have provided important insights into how virus-infected macrophages cause brain injury. Indeed, the stereotactic inoculation of HIV infected monocytes into the basal ganglia/cortex of mice with severe combined immunodeficiency disease (SCID) results in pathological features similar to those of human HIV-1 encephalitis (HIVE). We used this SCID model to study the roles of macrophage secretory factors in HIVE. The expression of interleukin-1 (IL-1β, IL-6, IL-10), tumor necrosis factor-alpha (TNFα), vascular endothelial growth factor (VEGF), and adhesion molecules (E-selectin, intracellular cell adhesion molecule (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1)) in encephalitic brains of mice and humans was evaluated by semi-quantitative polymerase chain reaction (PCR). In SCID mice with HIVE, human and mouse TNFα, and mouse IL-6, VEGF, VCAM-1 and E-selectin were expressed at high levels. These results paralleled, to a great extent, those in HIVE brain tissues. Laser scanning confocal microscopy performed to assess the associated neuronal damage showed that microtubule associated protein-2 (MAP-2) immunoreactive dendrites were significantly reduced in both the ipsilateral and contralateral hemispheres of encephalitic mice. These results demonstrate the importance of macrophage inflammatory products in the pathogenesis of HIVE and further validates this model of viral encephalitis in SCID mice.

Original languageEnglish (US)
Pages (from-to)401-416
Number of pages16
JournalJournal of neurovirology
Volume3
Issue number6
DOIs
StatePublished - Dec 1997

Fingerprint

Severe Combined Immunodeficiency
Encephalitis
HIV-1
Brain
Macrophages
E-Selectin
Vascular Cell Adhesion Molecule-1
Phagocytes
Interleukin-1
Vascular Endothelial Growth Factor A
Dementia
Tumor Necrosis Factor-alpha
Viral Encephalitis
Microtubule-Associated Proteins
Cell Adhesion Molecules
Microglia
Intercellular Adhesion Molecule-1
Dendrites
Basal Ganglia
Confocal Microscopy

Keywords

  • Animal model
  • HIV encephalitis
  • Inflammatory products
  • Neuronal damage
  • Neurotoxins

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

Cite this

An analysis of HIV-1-associated inflammatory products in brain tissue of humans and SCID mice with HIV-1 encephalitis. / Persidsky, Yuri; Buttini, Manuel; Limoges, Jenae; Bock, Paul; Gendelman, Howard Eliot.

In: Journal of neurovirology, Vol. 3, No. 6, 12.1997, p. 401-416.

Research output: Contribution to journalArticle

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