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Exogenous tat protein activates central nervous system-derived endothelial cells
F M Hofman1, M M Dohadwala, A D Wright
1Department of Pathology, University of Southern California School of Medicine, Los Angeles 90033.
Journal of Neuroimmunology
|October 1, 1994
Summary
Human Immunodeficiency Virus (HIV) Tat protein may facilitate HIV entry into the brain. Tat activates brain endothelial cells and alters the blood-brain barrier, potentially increasing infected cell migration into the central nervous system (CNS).
Area of Science:
- Neurovirology
- Immunology
- Cell Biology
Background:
- Human Immunodeficiency Virus (HIV) can infect the central nervous system (CNS).
- The HIV Tat protein is secreted extracellularly and is implicated in viral pathogenesis.
- Understanding mechanisms of HIV CNS entry is crucial for therapeutic development.
Purpose of the Study:
- To investigate the role of the HIV Tat protein in the dissemination of HIV into the CNS.
- To determine how Tat protein affects human CNS-derived endothelial cells (CNS-EC).
Main Methods:
- Activation of CNS-EC by Tat protein was assessed by measuring E-selectin expression, Interleukin-6 (IL-6) synthesis, and plasminogen activator inhibitor-1 (PAI-1) secretion.
- Synergistic effects of Tat with tumor necrosis factor alpha (TNF) were evaluated.
- In situ staining of AIDS brains for Tat protein was performed.
Main Results:
- Tat protein increased E-selectin expression, IL-6 synthesis, and PAI-1 secretion in CNS-EC.
- Tat protein exhibited synergistic activity with TNF.
- Positive staining for Tat was observed in cells within AIDS brains.
Conclusions:
- Secreted Tat protein may enhance leukocyte binding to the blood-brain barrier.
- Tat protein may alter blood-brain barrier permeability.
- These actions of Tat protein could facilitate the dissemination of HIV-infected cells into the CNS.