• Open Access

Infection of human pericytes by HIV-1 disrupts the integrity of the blood–brain barrier

Authors

  • Shinsuke Nakagawa,

    1. Molecular Neuroscience and Vascular Biology Laboratory, Department of Neurosurgery, University of Kentucky Medical Center, Lexington, KY, USA
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  • Victor Castro,

    1. Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Miami, FL, USA
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  • Michal Toborek

    Corresponding author
    1. Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Miami, FL, USA
    • Molecular Neuroscience and Vascular Biology Laboratory, Department of Neurosurgery, University of Kentucky Medical Center, Lexington, KY, USA
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Correspondence to: Michal TOBOREK, M.D., Ph.D., Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, R. Bunn Gautier Bldg., Room 517, 1011 NW 15th Street, Miami, FL 33136, USA.

Tel.: +305-243-0230

Fax: +305-243-3955

E-mail: mtoborek@med.miami.edu

Abstract

Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) affects cross-talk between the individual cell types of the neurovascular unit, which then contributes to disruption of the blood–brain barrier (BBB) and the development of neurological dysfunctions. Although the toxicity of HIV-1 on neurons, astrocytes and brain endothelial cells has been widely studied, there are no reports addressing the influence of HIV-1 on pericytes. Therefore, the purpose of this study was to evaluate whether or not pericytes can be infected with HIV-1 and how such an infection affects the barrier function of brain endothelial cells. Our results indicate that human brain pericytes express the major HIV-1 receptor CD4 and co-receptors CXCR4 and CCR5. We also determined that HIV-1 can replicate, although at a low level, in human brain pericytes as detected by HIV-1 p24 ELISA. Pericytes were susceptible to infection with both the X4-tropic NL4-3 and R5-tropic JR-CSF HIV-1 strains. Moreover, HIV-1 infection of pericytes resulted in compromised integrity of an in vitro model of the BBB. These findings indicate that human brain pericytes can be infected with HIV-1 and suggest that infected pericytes are involved in the progression of HIV-1-induced CNS damage.

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