Cocaine Increases Human Immunodeficiency Virus Type 1 Neuroinvasion Through Remodeling Brain Microvascular Endothelial Cells

Overview

Journal J Neurovirol

Publisher Springer

Specialties Microbiology
Neurology

Date 2005 Jul 23

PMID 16036808

Citations 49

Authors

Milan Fiala

Amy J Eshleman

John Cashman

Justin Lin

Albert S Lossinsky

Vannina Suarez

Wendy Yang

Jun Zhang

Waldemar Popik

Elyse Singer

Francesco Chiappelli

Eva Carro

Martin Weinand

Marlys Witte

James Arthos

Affiliations

Soon will be listed here.

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.

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