Human immunodeficiency virus type 1 Tat-mediated cytotoxicity of human brain microvascular endothelial cells

Naveed Ahmed Khan, Francescopaolo Di Cello, Avi Nath, Kwang Sik Kim

Research output: Contribution to journalReview articlepeer-review

Abstract

Human immunodeficiency virus (HIV)-1 infection is often complicated with neurologic disorders, but the pathogenesis of HIV-1 encephalopathy is incompletely understood. Tat (HIV-1 transactivator protein) is released from HIV-1-infected cells and has been detected in the sera and cerebrospinal fluid of HIV-1-infected patients. Tat, along with increased inflammatory cytokines such as interferon-gamma (IFN-γ), have been implicated in the pathogenesis of HIV-1-associated blood-brain barrier dysfunction. The present study examined the effects of Tat and IFN-γ on human brain microvascular endothelial cells (HB-MECs), which constitute the blood-brain barrier. Tat produced cytotoxicity of HBMECs, but required IFN-γ. IFN-γ treatment of HBMECs up-regulates vascular endothelial growth factor receptor-2 (VEGFR2/KDR), which is known to be the receptor for Tat. Tat activated KDR in the presence of IFN-γ, and Tat-mediated cytopathic changes involve its interaction with KDR and phosphatidylinositol 3-kinase (PI3K). Further understanding and characterization of Tat-HBMEC interactions should help us understand HIV-1 neuropathogenesis and develop strategies to prevent HIV-1 encephalopathy.

Original languageEnglish (US)
Pages (from-to)584-593
Number of pages10
JournalJournal of neurovirology
Volume9
Issue number6
DOIs
StatePublished - Dec 2003

Keywords

  • Human brain microvascular endothelial cells
  • IFN-gamma
  • PI3K
  • Tat
  • VEGFR2/KDR

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

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