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

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 E Weinand, Marlys H Witte, James Arthos

Research output: Contribution to journalArticle

55 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)281-291
Number of pages11
JournalJournal of NeuroVirology
Volume11
Issue number3
DOIs
StatePublished - Jul 2005

Fingerprint

Cocaine
HIV-1
Endothelial Cells
Brain
Benztropine
Viruses
Cocaine-Related Disorders
Biogenic Amines
Intercellular Junctions
Muscarinic Receptors
Tamoxifen
Lakes
Lysosomes
Blood-Brain Barrier
Cytoskeleton
Electric Impedance
Cell Adhesion
Dementia
Permeability
Signal Transduction

Keywords

  • Brain microvascular endothelial cells
  • Cocaine
  • HIV-1
  • HIV-1 macropinocytosis

ASJC Scopus subject areas

  • Virology
  • Clinical Neurology

Cite this

Cocaine increases human immunodeficiency virus type 1 neuroinvasion through remodeling brain microvascular endothelial cells. / Fiala, Milan; Eshleman, Amy J.; Cashman, John; Lin, Justin; Lossinsky, Albert S.; Suarez, Vannina; Yang, Wendy; Zhang, Jun; Popik, Waldemar; Singer, Elyse; Chiappelli, Francesco; Carro, Eva; Weinand, Martin E; Witte, Marlys H; Arthos, James.

In: Journal of NeuroVirology, Vol. 11, No. 3, 07.2005, p. 281-291.

Research output: Contribution to journalArticle

Fiala, M, Eshleman, AJ, Cashman, J, Lin, J, Lossinsky, AS, Suarez, V, Yang, W, Zhang, J, Popik, W, Singer, E, Chiappelli, F, Carro, E, Weinand, ME, Witte, MH & Arthos, J 2005, 'Cocaine increases human immunodeficiency virus type 1 neuroinvasion through remodeling brain microvascular endothelial cells', Journal of NeuroVirology, vol. 11, no. 3, pp. 281-291. https://doi.org/10.1080/13550280590952835
Fiala, Milan ; Eshleman, Amy J. ; Cashman, John ; Lin, Justin ; Lossinsky, Albert S. ; Suarez, Vannina ; Yang, Wendy ; Zhang, Jun ; Popik, Waldemar ; Singer, Elyse ; Chiappelli, Francesco ; Carro, Eva ; Weinand, Martin E ; Witte, Marlys H ; Arthos, James. / Cocaine increases human immunodeficiency virus type 1 neuroinvasion through remodeling brain microvascular endothelial cells. In: Journal of NeuroVirology. 2005 ; Vol. 11, No. 3. pp. 281-291.
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