Development of laboratory and animal model systems for HIV-1 encephalitis and its associated dementia

Yuri Persidsky, Howard Eliot Gendelman

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

The neuropathogenesis of HIV-1 encephalitis and its associated dementia revolves around sustained viral replication in cells of mononuclear phagocyte origin (brain macrophages, multinucleated giant cells, and microglia). Macrophage secretory factors play important roles in facilitating monocyte trafficking into the brain, in regulating productive viral replication, and in producing neurotoxic responses. To study these events, we constructed an artificial blood-brain barrier (BBB) to assay monocyte transendothelial migration and developed an animal model system for HIV-1 encephalitis to ascertain the role that virus-infected mononuclear phagocytes play in disease pathogenesis. The BBB model was composed of brain microvascular endothelial cells and astrocytes placed on opposite sides of a porous membrane. Monocyte activation, not HIV-1 infection per se, was the central event affecting monocyte BBB migration. Many of the pathological features of HIV-1 encephalitis were reproduced in SCID mice stereotactically inoculated with virus-infected monocytes. These included widespread astrogliosis, apoptosis of neurons, dendritic damage, and macrophage/microglial activation. Such laboratory and animal model systems are being used to ascertain the pathogenic potential of virus-infected macrophages in brain and ways to curb such injurious effects.

Original languageEnglish (US)
Pages (from-to)100-106
Number of pages7
JournalJournal of Leukocyte Biology
Volume62
Issue number1
DOIs
Publication statusPublished - Jul 1997

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Keywords

  • Blood-brain barrier
  • Macrophage

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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