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

Georgette D. Kanmogne, R. C. Kennedy, Paula Grammas

Research output: Contribution to journalArticle

64 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)992-1000
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Volume61
Issue number11
DOIs
StatePublished - Nov 1 2002

    Fingerprint

Keywords

  • Brain endothelial cells
  • HIV-1
  • HIV-associated dementia
  • Neurons
  • gp120 proteins
  • gp160 peptides

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this