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PMID: 9525661 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Human immunodeficiency virus neurotropism: an analysis of viral replication and cytopathicity for divergent strains in monocytes and microglia.

Journal of virology ·Vol. 72 ·No. 4 ·1998-04-00 ·Pages 3340-50

Ghorpade A, Nukuna A, Che M, Haggerty S, Persidsky Y, Carter E, Carhart L, Shafer L, Gendelman HE

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.

MeSH Terms
Cells, Cultured Cytopathogenic Effect, Viral DNA Replication DNA, Viral/biosynthesis Fluorescent Antibody Technique, Indirect HIV-1/genetics,growth & development,isolation & purification,physiology Humans Microglia/cytology,virology Monocytes/cytology,virology Virion Virus Replication
Chemicals
DNA, Viral
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Ghorpade A
Center for Neurovirology and Neurodegenerative Disorders and the Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198, USA.
Nukuna A
Che M
Haggerty S
Persidsky Y
Carter E
Carhart L
Shafer L
Gendelman H E
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.72.4.3340-3350.1998
Published
1998-04-00
Pages
3340-50
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC109814
Subset
IM
Grants
NINDS NIH HHS · R01 NS036126 · United States
NINDS NIH HHS · R01 NS34239-04 · United States
NINDS NIH HHS · P01 NS031492 · United States
NINDS NIH HHS · 1 R01 NS36126-01 · United States
NINDS NIH HHS · P01 NS31492-05 · United States
NINDS NIH HHS · R01 NS034239 · United States
External Links
PubMed source DOI: 10.1128/JVI.72.4.3340-3350.1998 PMC Full Text View journal details
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