Human Immunodeficiency Virus Neurotropism: an Analysis of Viral Replication and Cytopathicity for Divergent Strains in Monocytes and Microglia

Authors

• Anuja Ghorpade, University of Nebraska Medical Center
• Adeline Nukuna, University of Nebraska Medical Center
• Myhanh Che, University of Nebraska Medical Center
• Sherryl Haggerty, University of Nebraska Medical Center
• Yuri Persidsky, University of Nebraska Medical Center
• Eboni Carter, University of Nebraska Medical Center
• Leeroy Carhart, University of Nebraska Medical Center
• Laura Shafer, University of Nebraska Medical Center
• Howard Gendelman, University of Nebraska Medical Center & Nebraska Center for VirologyFollow

Document Type

Article

Date of this Version

April 1998

Comments

Published in JOURNAL OF VIROLOGY, Apr. 1998, p. 3340–3350 Vol. 72, No. 4, 0022-538X/98/$04.0010 Copyright © 1998, American Society for Microbiology. Used by permission.

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-1BAL (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.