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

Shinsuke Nakagawa, Victor Castro, Michal Toborek

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2950-2957
Number of pages8
JournalJournal of Cellular and Molecular Medicine
Volume16
Issue number12
DOIs
StatePublished - Dec 2012

Keywords

  • Blood-brain barrier
  • HIV-1
  • Neurovascular unit
  • Pericytes

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

Fingerprint Dive into the research topics of 'Infection of human pericytes by HIV-1 disrupts the integrity of the blood-brain barrier'. Together they form a unique fingerprint.

Cite this