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Original

Cocaine increases human immunodeficiency virus type 1 neuroinvasion through remodeling brain microvascular endothelial cells

, , , , , , , , , , , , , & show all
Pages 281-291 | Received 06 Dec 2004, Accepted 08 Feb 2005, Published online: 10 Jul 2009
 

Abstract

Cocaine is a suspected cofactor in human immunodeficiency virus (HIV)-associated dementia but cocaine's effects are not clear. Herein the authors describe investigations of the mechanisms by which cocaine increases HIV-1 invasion through brain microvascular endothelial cells (BMVECs). Cocaine binds to a site on BMVECs, which is not a biogenic amine transporter, a binding site for estrogen, or a muscarinic receptor and for which benztropine and tamoxifen have the highest affinity. Cocaine treatment of BMVECs disrupts intercellular junctions and induces cell ruffling, which could account for their increased permeability and decreased electrical resistance. HIV-1 enters BMVECs by macropinocytosis and is transported to lysosomes and inactivated. In cocaine-treated BMVECs, the virus enters and persists in large cytoplasmic “lakes.” Cocaine exposure of BMVECs up-regulates transcription of genes important in cytoskeleton organization, signal transduction, cell swelling, vesicular trafficking, and cell adhesion. The toxicity of cocaine for the blood-brain barrier may lead to increased virus neuroinvasion and neurovascular complications of cocaine abuse. Journal of NeuroVirology (2005) 11, 281–291.

This work was supported by National Institutes of Health grants DA10442, HL63639, and HK63065 to M.F., AI42557 and AI50461 to W.P., and HL48493 to M.W. The Manhattan HIV Brain Bank, New York, and the National Neurological AIDS Brain Bank at UCLA, Los Angeles, of the National NeuroAIDS Tissue Consortium provided the brain tissues. The AIDS Research and Reference Reagent Program, NIAID, National Institutes of Health, provided the listed antibodies.We appreciate discussions with P. Shapshak, University of Miami, regarding complications of cocaine abuse. Daniel Mcelligot, (VizX, GeneSifter Inc.) provided excellent technical support with the analysis of microarray data.

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