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

J Cell Mol Med. 2012 Dec;16(12):2950-7. doi: 10.1111/j.1582-4934.2012.01622.x.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Astrocytes / physiology
  • Astrocytes / virology
  • Blood-Brain Barrier / physiology*
  • Blood-Brain Barrier / virology
  • Brain / blood supply*
  • Brain / cytology
  • Brain / virology
  • CD4 Antigens / metabolism
  • Cells, Cultured
  • Endothelial Cells / virology
  • HIV Core Protein p24 / metabolism
  • HIV Infections*
  • HIV-1 / physiology*
  • Humans
  • Interleukin-6 / biosynthesis
  • Nervous System Diseases / virology
  • Pericytes / physiology*
  • Pericytes / virology*
  • Receptors, CCR5 / metabolism
  • Receptors, CXCR4 / metabolism
  • Virus Replication

Substances

  • CD4 Antigens
  • CXCR4 protein, human
  • HIV Core Protein p24
  • Interleukin-6
  • Receptors, CCR5
  • Receptors, CXCR4