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Development of laboratory and animal model systems for HIV‐1 encephalitis and its associated dementia
Author(s) -
Persidsky Yuri,
Gendelman Howard E.
Publication year - 1997
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.62.1.100
Subject(s) - biology , human immunodeficiency virus (hiv) , dementia , animal model , encephalitis , virology , neuroscience , immunology , cognitive science , disease , virus , pathology , psychology , medicine , endocrinology
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. J. Leukoc. Biol . 62: 100–106; 1997.