HIV-1 gp120 proteins and gp160 peptides are toxic to brain endothelial cells and neurons: possible pathway for HIV entry into the brain and HIV-associated dementia

J Neuropathol Exp Neurol. 2002 Nov;61(11):992-1000. doi: 10.1093/jnen/61.11.992.

Abstract

Breakdown of the blood-brain barrier is commonly seen in patients with human immunodeficiency virus (HIV)-associated dementia, despite the lack of productive HIV-infection of the brain endothelium. Through this damaged blood-brain barrier, HIV and HIV-infected monocytes/macrophages infiltrate the brain and further infect microglia and brain macrophages. Neuronal cell death and dysfunction are the underlying cause of HIV-associated dementia, but no productive HIV-infection of neurons has been documented. It is likely that secreted viral products play a major role in blood-brain barrier damage and neuronal cell death. The aim of the present study was to examine the effect of HIV-1 gp160 peptides and gp120 proteins on brain microvascular endothelial cells and neurons from both human and rats. Four of the 7 gp160 peptides tested evoked significant neurotoxicity. Two different full-length recombinant HIV gp120 proteins (HIV-1CM235 gp120 and HIV-1MN gp120) also induced neuronal and brain endothelial cell death, and concentrations as little as 1 ng/ml evoked pronounced morphological changes in these cells and marked cytotoxicity. This study suggests that HIV proteins and peptides that are shed in vivo may be directly involved in blood-brain barrier damage and neuronal cell death in HIV-associated dementia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS Dementia Complex / immunology
  • AIDS Dementia Complex / metabolism*
  • AIDS Dementia Complex / virology
  • Animals
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / immunology*
  • Brain / immunology
  • Brain / metabolism
  • Brain / virology
  • Cell Death / drug effects
  • Cell Death / immunology
  • Cells, Cultured
  • Culture Media, Conditioned / pharmacology
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / virology
  • Fetus
  • HIV Envelope Protein gp120 / metabolism*
  • HIV Envelope Protein gp120 / toxicity
  • HIV Envelope Protein gp160 / metabolism*
  • HIV Envelope Protein gp160 / toxicity
  • HIV-1 / metabolism*
  • HIV-1 / pathogenicity
  • Humans
  • Monocytes / metabolism
  • Monocytes / virology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neurons / virology
  • Peptide Fragments / toxicity
  • Rats
  • Recombinant Fusion Proteins / toxicity

Substances

  • Culture Media, Conditioned
  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp160
  • Peptide Fragments
  • Recombinant Fusion Proteins