HIV-1 Tat protein alters tight junction protein expression and distribution in cultured brain endothelial cells

Ibolya E. András, Hong Pu, Mária A. Deli, Avindra Nath, Bernhard Hennig, Michal Toborek

Research output: Contribution to journalArticle

125 Scopus citations

Abstract

Disruption of the blood-brain barrier (BBB) is widely believed to be the main route of human immunodeficiency virus (HIV) entry into the central nervous system (CNS). Although mechanisms of this process are not fully understood, alterations of tight junction protein expression can contribute, at least in part, to this phenomenon. Tight junctions are critical structural and functional elements of cerebral microvascular endothelial cells and the BBB. The aim of the present study was to examine the effects of HIV-1 Tat protein on expression of tight junction proteins. Primary cultures of brain microvascular endothelial cells (BMEC) were employed in these experiments. A 24-hr exposure of BMEC to Tat1-72 resulted in a decrease of claudin-1, claudin-5, and zonula occludens (ZO)-2 expression, whereas total levels of occludin and ZO-1 remained unchanged. In addition, a short (3-hr) exposure of BMEC to Tat1-72 induced cellular redistribution of claudin-5 immunoreactivity. Tat1-72-induced alterations of claudin-5 expression also were confirmed in vivo where Tat1-72 was injected into the right hippocampus of mice. These findings indicate that HIV-1 Tat protein can markedly affect expression and distribution of specific tight junction proteins in brain endothelium. Alterations of only distinct tight junction proteins suggest a finely tuned effect of Tat1-72 on the BBB. Because tight junction proteins are critical for the barrier function of the BBB, such alterations can lead to disturbances of the BBB integrity and contribute to HIV trafficking into the brain.

Original languageEnglish (US)
Pages (from-to)255-265
Number of pages11
JournalJournal of Neuroscience Research
Volume74
Issue number2
DOIs
StatePublished - Oct 15 2003
Externally publishedYes

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Keywords

  • Blood-brain barrier
  • Brain endothelial cell dysfunction
  • HIV/AIDS
  • Tight junction proteins
  • Viral proteins

ASJC Scopus subject areas

  • Neuroscience(all)

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