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.