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J Virol, April 1998, p. 3340-3350, Vol. 72, No. 4
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

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

Anuja Ghorpade, Adeline Nukuna, MyHanh Che, Sheryl Haggerty, Yuri persidsky, eboni carter, leeroy carhart, laura shafer, and Howard E. Gendelman*

Center for Neurovirology and Neurodegenerative Disorders and the Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198

Received 28 August 1997/Accepted 30 December 1997

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-1ADA and HIV-189.6 (from peripheral blood mononuclear cells), HIV-1DJV and HIV-1JR-FL (from brain tissue), HIV-1SF162 (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.

* Corresponding author. Mailing address: Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, 600 S. 42nd St., Box 985215, Omaha, NE 68198-5215. Phone: (402) 559-8926. Fax: (402) 559-8922. E-mail: hegendel{at}mail.unmc.edu.




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