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

Abstract

HIV‐1 infection of the brain affects the cross‐talk between the individual cell types of the neurovascular unit, which then contributes to the disruption of the blood‐brain barrier (BBB) and the development of neurological dysfunctions. While 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 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 coreceptors CXCR4 and CCR5. Importantly, we demonstrate for the first time that HIV‐1 can replicate, though at a low level, in human brain pericytes. Pericytes are susceptible to infection with both the X4‐tropic and R5‐tropic HIV‐1 strains. Moreover, HIV‐1 infection of pericytes results in compromised integrity of the in vitro model of the BBB. These findings suggest that infected pericytes may be involved in progression of HIV‐1‐induced CNS damage. Supported by MH63022, MH072567, DA027569, NS39254, and ES 07380.