Cocaine increases human immunodeficiency virus type 1 neuroinvasion through remodeling brain microvascular endothelial cells (original) (raw)

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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Authors and Affiliations

1. Department of Medicine, West Los Angeles VA Medical Center, Los Angeles, California
   Milan Fiala, Justin Lin, Vannina Suarez & Wendy Yang
2. UCLA Oral Biology and Medicine, CHS 63-090, 10833 Le Conte, 90095, Los Angeles, CA, USA
   Milan Fiala, Justin Lin, Vannina Suarez & Wendy Yang
3. Department of Pharmacology, VA Medical Center, Portland, Oregon, USA
   Amy J. Eshleman
4. Human BioMolecular Research Institute, San Diego, California, USA
   John Cashman & Jun Zhang
5. Huntington Medical Research Institutes, Pasadena, California, USA
   Albert S. Lossinsky
6. Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
   Waldemar Popik
7. Department of Neurology, UCLA School of Medicine, Los Angeles, California, USA
   Elyse Singer
8. Department of Oral Biology and Medicine, UCLA School of Dentistry, Los Angeles, California, USA
   Francesco Chiappelli
9. Laboratory of Neuroendocrinology, Cajal Institute, CSIC, Madrid, Spain
   Eva Carro
10. Department of Surgery, University of Arizona, Tucson, Arizona, USA
    Martin Weinand & Marlys Witte
11. Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
    James Arthos

Authors

1. Milan Fiala
2. Amy J. Eshleman
3. John Cashman
4. Justin Lin
5. Albert S. Lossinsky
6. Vannina Suarez
7. Wendy Yang
8. Jun Zhang
9. Waldemar Popik
10. Elyse Singer
11. Francesco Chiappelli
12. Eva Carro
13. Martin Weinand
14. Marlys Witte
15. James Arthos

Corresponding author

Correspondence toMilan Fiala.

Additional information

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.

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Fiala, M., Eshleman, A.J., Cashman, J. et al. Cocaine increases human immunodeficiency virus type 1 neuroinvasion through remodeling brain microvascular endothelial cells.Journal of NeuroVirology 11, 281–291 (2005). https://doi.org/10.1080/13550280590952835

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• Received: 06 December 2004
• Revised: 01 February 2005
• Accepted: 08 February 2005
• Issue date: May 2005
• DOI: https://doi.org/10.1080/13550280590952835

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