Maturing neurons are selectively sensitive to human immunodeficiency virus type 1 exposure in differentiating human neuroepithelial progenitor cell cultures

Micheline McCarthy, Irving Vidaurre, Rebeca Geffin

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Human immunodeficiency virus type 1 (HIV-1) infection of the brain is associated with neuronal injury manifested by dendritic pruning, aberrant neurofilament metabolism, and decreased synaptic density. The central nervous system (CNS) responds to neuronal injury by differentiating new neurons and astrocytes from resident populations of multipotent neuroepithelial progenitor cells (NEP) located in regions such as the subventricular zone or hippocampus. In vitro studies have demonstrated that the HIV-1 virion or envelope glycoprotein gp120 can injure differentiated human neurons and astrocytes, suggesting that HIV-1 proteins could similarly injure NEP or NEP-derived glial and neuronal lineage-committed precursor cells. To answer this question, human fetal brain-derived "neurospheres" containing NEP and NEP-derived precursor cells were cultured in low serum differentiation medium containing lymphotropic HIV-1(SF2), macrophage-tropic HIV-1(SF128A), or recombinant gp120SF2 from HIV-1(SF2). These experiments indicate that exposure to HIV-1 does not affect the ability of the NEP to differentiate into cells expressing either astrocyte-specific or neuron-specific cytoskeletal antigens. However prolonged exposure to HIV-1 does selectively decrease expression of neuronal antigens (microtubule β-III-tubulin and intermediate filament neurofilament-L) but not astrocyte antigens (intermediate filament glial fibrillary acidic protein). The effects of continuous exposure to HIV-1 or gp120 may result from injury to developing neurons and/or impairment of the neuronal developmental process itself. By depressing neuronal microtubule and neurofilament protein expression, HIV-1 and gp120 exposure compromise the potential for postmitotic neuronal dendrite and axon development.

Original languageEnglish (US)
Pages (from-to)333-348
Number of pages16
JournalJournal of neurovirology
Volume12
Issue number5
DOIs
StatePublished - Oct 1 2006

Keywords

  • Cell differentiation
  • HIV envelope protein gp120
  • HIV-1
  • Neuroepithelial cells
  • Neurofilament proteins
  • Oxidative stress

ASJC Scopus subject areas

  • Virology
  • Clinical Neurology

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