HIV-1 activates proinflammatory and interferon-inducible genes in human brain microvascular endothelial cells: putative mechanisms of blood-brain barrier dysfunction.
The mechanisms underlying blood-brain barrier (BBB) dysfunction seen in human immunodeficiency virus 1 (HIV-1) infection are poorly understood; however, they are believed to be caused by interactions of human brain microvascular endothelial cells (HBMEC) with virus-infected macrophages. Using a transwell system and Affymetrix arrays, we investigated HIV-1-induced genomic changes in HBMEC after coculture with HIV-1-infected or -uninfected monocyte-derived macrophages (MDM). Differentially expressed genes were determined by linear modeling and then were grouped by hierarchical clustering. Compared to HBMEC cocultured with noninfected MDM, 184 probe sets corresponding to 84 genes were differentially expressed in HBMEC cocultured with HIV-infected MDM. Genes activated in HIV-1 MDM-exposed HBMEC included proinflammatory cytokines and chemokines, tumor necrosis factor-alpha-induced proteins, interferon (IFN)-inducible genes, intercellular adhesion molecule-1, transcription factors of the nuclear factor-kappaB family, and signal transducer and activator of transcription 1. Analysis of molecular networks and canonical pathways associated with differentially expressed genes suggest that HIV-1 causes BBB impairment by mechanisms involving inflammation, cytokine, and IFN signaling in HBMEC.
Chaudhuri
Anathbandhu
A
Department of Pharmacology and Experimental Neuroscience, Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, Nebraska 68198-5215, USA.
Duan
Fenghai
F
Morsey
Brenda
B
Persidsky
Yuri
Y
Kanmogne
Georgette D
GD
D001812:Blood-Brain Barrier / Q000502:physiology / Q000821:virology*; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000502:physiology / Q000821:virology*; D015870:Gene Expression; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000503:physiopathology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000821:virology*; D007372:Interferons / Q000502:physiology*; D008264:Macrophages / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007372:Interferons