title: Analysis of human endothelial cells and cortical neurons for susceptibility to HIV-1 infection and co-receptor expression.
abstract: Neuronal cell death is believed to be the underlying cause of neurological diseases and AIDS dementia often seen in human immunodeficiency virus (HIV) infected patients. The means by which HIV invades the brain is still unknown and the mechanism of neuronal cell death remains to be elucidated. The aim of this study was to determine if direct infection of human brain endothelial cells and neurons play a role in viral invasion of the brain and neuronal cell death, respectively. To this effect, we evaluated human brain microvascular endothelial cells (HBMEC) and human cortical neurons (HCN) for the expression of HIV co-receptors and their susceptibility to HIV-1 infection. While both HBMEC and HCN failed to express any CXCR4 and CCR5 on their cell surface, as assessed by flow cytometry, RT - PCR revealed the presence of CXCR4 and CCR5 mRNA in HBMEC but not in HCN. Two dual tropic HIV-1 primary isolates failed to infect both cell types as determined by p24 antigen capture ELISA, RT - PCR and DNA PCR. These data support the hypothesis that no productive infection of HBMEC and HCN occurs in vitro and suggest that other cell types are the primary focus of HIV-1 infection in the brain.
authors.affiliation: Department of Microbiology & Immunology, University of Oklahoma Health Sciences Center, 975 NE 10th Street, Biomedical Research Center, Oklahoma City, OK 73104, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Kanmogne
authors.forename: P
authors.initials: P
authors.lastname: Grammas
authors.forename: R C
authors.initials: RC
authors.lastname: Kennedy
mesh_terms: D001921:Brain / Q000098:blood supply* / Q000166:cytology; D002196:Capillaries / Q000166:cytology; D002478:Cells, Cultured; D004198:Disease Susceptibility; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D009474:Neurons / Q000378:metabolism / Q000821:virology*; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D012680:Sensitivity and Specificity
chemical_list: D016655:HIV Core Protein p24; D012333:RNA, Messenger; D019713:Receptors, CCR5; D019718:Receptors, CXCR4