title: Infection of human pericytes by HIV-1 disrupts the integrity of the blood-brain barrier.
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.
authors.affiliation: Molecular Neuroscience and Vascular Biology Laboratory, Department of Neurosurgery, University of Kentucky Medical Center, Lexington, KY, USA.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Victor
authors.initials: V
authors.lastname: Castro
authors.forename: Michal
authors.initials: M
authors.lastname: Toborek
mesh_terms: D001253:Astrocytes / Q000502:physiology / Q000821:virology; D001812:Blood-Brain Barrier / Q000502:physiology* / Q000821:virology; D001921:Brain / Q000098:blood supply* / Q000166:cytology / Q000821:virology; D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000821:virology; D016655:HIV Core Protein p24 / Q000378:metabolism; D015658:HIV Infections; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D009422:Nervous System Diseases / Q000821:virology; D020286:Pericytes / Q000502:physiology* / Q000821:virology*; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D014779:Virus Replication
chemical_list: D015704:CD4 Antigens; C527276:CXCR4 protein, human; D016655:HIV Core Protein p24; D015850:Interleukin-6; D019713:Receptors, CCR5; D019718:Receptors, CXCR4