title: Human immunodeficiency virus neurotropism: an analysis of viral replication and cytopathicity for divergent strains in monocytes and microglia.
abstract: 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 viral 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-1(89.6) (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 microglia 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-1 to invade, replicate, and incite disease within its microglial target cells.
authors.affiliation: Center for Neurovirology and Neurodegenerative Disorders and the Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198, USA.
authors.forename: A
authors.initials: A
authors.lastname: Ghorpade
authors.forename: A
authors.initials: A
authors.lastname: Nukuna
authors.forename: M
authors.initials: M
authors.lastname: Che
authors.forename: S
authors.initials: S
authors.lastname: Haggerty
authors.forename: Y
authors.initials: Y
authors.lastname: Persidsky
authors.forename: E
authors.initials: E
authors.lastname: Carter
authors.forename: L
authors.initials: L
authors.lastname: Carhart
authors.forename: L
authors.initials: L
authors.lastname: Shafer
authors.forename: H E
authors.initials: HE
authors.lastname: Gendelman
mesh_terms: D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral; D004261:DNA Replication; D004279:DNA, Viral / Q000096:biosynthesis; D019084:Fluorescent Antibody Technique, Indirect; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D017628:Microglia / Q000166:cytology / Q000821:virology*; D009000:Monocytes / Q000166:cytology / Q000821:virology*; D014771:Virion; D014779:Virus Replication
chemical_list: D004279:DNA, Viral