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HIV-1 Tat protein alters tight junction protein expression and distribution in cultured brain endothelial cells.
J Neurosci Res 2003; 74(2):255-65JN

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 Tat(1-72) 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 Tat(1-72) induced cellular redistribution of claudin-5 immunoreactivity. Tat(1-72)-induced alterations of claudin-5 expression also were confirmed in vivo where Tat(1-72) 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 Tat(1-72) 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.

Authors+Show Affiliations

Department of Surgery, University of Kentucky, Lexington, Kentucky, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14515355

Citation

András, Ibolya E., et al. "HIV-1 Tat Protein Alters Tight Junction Protein Expression and Distribution in Cultured Brain Endothelial Cells." Journal of Neuroscience Research, vol. 74, no. 2, 2003, pp. 255-65.
András IE, Pu H, Deli MA, et al. HIV-1 Tat protein alters tight junction protein expression and distribution in cultured brain endothelial cells. J Neurosci Res. 2003;74(2):255-65.
András, I. E., Pu, H., Deli, M. A., Nath, A., Hennig, B., & Toborek, M. (2003). HIV-1 Tat protein alters tight junction protein expression and distribution in cultured brain endothelial cells. Journal of Neuroscience Research, 74(2), pp. 255-65.
András IE, et al. HIV-1 Tat Protein Alters Tight Junction Protein Expression and Distribution in Cultured Brain Endothelial Cells. J Neurosci Res. 2003 Oct 15;74(2):255-65. PubMed PMID: 14515355.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - HIV-1 Tat protein alters tight junction protein expression and distribution in cultured brain endothelial cells. AU - András,Ibolya E, AU - Pu,Hong, AU - Deli,Mária A, AU - Nath,Avindra, AU - Hennig,Bernhard, AU - Toborek,Michal, PY - 2003/9/30/pubmed PY - 2003/12/17/medline PY - 2003/9/30/entrez SP - 255 EP - 65 JF - Journal of neuroscience research JO - J. Neurosci. Res. VL - 74 IS - 2 N2 - 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 Tat(1-72) 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 Tat(1-72) induced cellular redistribution of claudin-5 immunoreactivity. Tat(1-72)-induced alterations of claudin-5 expression also were confirmed in vivo where Tat(1-72) 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 Tat(1-72) 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. SN - 0360-4012 UR - https://www.unboundmedicine.com/medline/citation/14515355/HIV_1_Tat_protein_alters_tight_junction_protein_expression_and_distribution_in_cultured_brain_endothelial_cells_ L2 - https://doi.org/10.1002/jnr.10762 DB - PRIME DP - Unbound Medicine ER -