HIV-1 gp120 proteins alter tight junction protein expression and brain endothelial cell permeability: implications for the pathogenesis of HIV-associated dementia.
Breakdown of the blood-brain barrier (BBB) is commonly seen in patients with HIV-associated dementia (HAD) despite the lack of productive infection of the brain endothelium. It is likely that secreted viral products play a major role in BBB damage and the development of HAD. The objective of this study is to determine the effects of gp120 proteins on brain endothelial cell permeability and junctional protein expression. Our results showed that treatment of cultured human brain endothelial cells with gp120 for 24 hours results in increased permeability of the endothelial monolayer. Also, gp120 proteins caused disruption and downregulation of the tight junction proteins ZO-1, ZO-2, and occludin in these cells. Other junctional proteins such as claudin-1 and claudin-5 were unaffected by gp120 treatment. These data demonstrate that HIV gp120 proteins alter both the functional and molecular properties of the BBB, which could increase trafficking of HIV, infected cells, and toxic humoral factors into the central nervous system and contribute to the pathogenesis of HAD.
Department of Pharmacology, Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, Nebraska 68198-5215, USA. gkanmogne@unmc.edu
Georgette D
GD
Kanmogne
Charles
C
Primeaux
Paula
P
Grammas
D000704:Analysis of Variance; D015153:Blotting, Western; D001921:Brain / Q000166:cytology*; D002478:Cells, Cultured; D003911:Dextrans / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects*; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008565:Membrane Proteins / Q000378:metabolism*; D062793:Occludin; D010539:Permeability / Q000187:drug effects; D010750:Phosphoproteins / Q000378:metabolism; D013997:Time Factors; D062826:Zonula Occludens-1 Protein; D062827:Zonula Occludens-2 Protein
D003911:Dextrans; D015699:HIV Envelope Protein gp120; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D010750:Phosphoproteins; C569042:TJP1 protein, human; C569046:TJP2 protein, human; D062826:Zonula Occludens-1 Protein; D062827:Zonula Occludens-2 Protein