TY - JOUR
T1 - Human immunodeficiency virus neurotropism
T2 - An analysis of vital replication and cytopathicity for divergent strains in monocytes and microgila
AU - Ghorpade, Anuja
AU - Nukuna, Adeline
AU - Che, Myhanh
AU - Haggerty, Sheryl
AU - Persidsky, Yuri
AU - Carter, Eboni
AU - Carhart, Leeroy
AU - Shafer, Laura
AU - Gendelman, Howard E.
PY - 1998/4
Y1 - 1998/4
N2 - Productive replication of human immunodeficiency virus type 1 (HIV-1) in brain macrophages and microglia is a critical component of viral neuropathogenesis. However, how virus-macrophage interactions lead to neurological disease remains incompletely understood. Possibly, a differential ability of virus to replicate in brain tissue macrophages versus macrophages in other tissues underlies HIV-1 neurovirulence. To these ends, we established systems for the isolation and propagation of pure populations of human microglia and then analyzed the vital life cycles of divergent HIV- 1 strains in these cells and in cultured monocytes by using identical viral inocula and indicator systems. The HIV-1 isolates included those isolated from blood, lung tissue, cerebrospinal fluids (CSF), and brain tissues of infected subjects: HIV-1(ADA) and HIV-189.6 (from peripheral blood mononuclear cells), HIV-1(DJV) and HIV-1(JR-FL) (from brain tissue), HIV- 1(SF162) (from CSF), and HIV-1(BAL) (from lung tissue). The synthesis of viral nucleic acids and viral mRNA, cytopathicity, and release of progeny virions were assessed. A significant heterogeneity among macrophage-tropic isolates for infection of monocytes and microgila was demonstrated. Importantly, a complete analysis of the viral life cycle revealed no preferential differences in the abilities of the HIV-1 strains tested to replicate in microglia and/or monocytes. Macrophage tropism likely dictates the abilities of HIV-I to invade, replicate, and incite disease within its microglial target cells.
AB - Productive replication of human immunodeficiency virus type 1 (HIV-1) in brain macrophages and microglia is a critical component of viral neuropathogenesis. However, how virus-macrophage interactions lead to neurological disease remains incompletely understood. Possibly, a differential ability of virus to replicate in brain tissue macrophages versus macrophages in other tissues underlies HIV-1 neurovirulence. To these ends, we established systems for the isolation and propagation of pure populations of human microglia and then analyzed the vital life cycles of divergent HIV- 1 strains in these cells and in cultured monocytes by using identical viral inocula and indicator systems. The HIV-1 isolates included those isolated from blood, lung tissue, cerebrospinal fluids (CSF), and brain tissues of infected subjects: HIV-1(ADA) and HIV-189.6 (from peripheral blood mononuclear cells), HIV-1(DJV) and HIV-1(JR-FL) (from brain tissue), HIV- 1(SF162) (from CSF), and HIV-1(BAL) (from lung tissue). The synthesis of viral nucleic acids and viral mRNA, cytopathicity, and release of progeny virions were assessed. A significant heterogeneity among macrophage-tropic isolates for infection of monocytes and microgila was demonstrated. Importantly, a complete analysis of the viral life cycle revealed no preferential differences in the abilities of the HIV-1 strains tested to replicate in microglia and/or monocytes. Macrophage tropism likely dictates the abilities of HIV-I to invade, replicate, and incite disease within its microglial target cells.
UR - http://www.scopus.com/inward/record.url?scp=0031949490&partnerID=8YFLogxK
U2 - 10.1128/jvi.72.4.3340-3350.1998
DO - 10.1128/jvi.72.4.3340-3350.1998
M3 - Article
C2 - 9525661
AN - SCOPUS:0031949490
SN - 0022-538X
VL - 72
SP - 3340
EP - 3350
JO - Journal of Virology
JF - Journal of Virology
IS - 4
ER -