HIV-1 infected monocyte-derived macrophages affect the human brain microvascular endothelial cell proteome: new insights into blood-brain barrier dysfunction for HIV-1-associated dementia.
Blood-brain barrier (BBB) compromise and transendothelial migration of HIV-infected leukocytes into the central nervous system (CNS) underlies the neuropathogenesis of HIV-1 infection. How this occurs is incompletely understood. We used a proteomic platform integrating difference gel electrophoresis and tandem mass spectrometry peptide sequencing to determine the effects that HIV-1-infected macrophages have on human brain microvascular endothelial cell (HBMEC) protein profiles. HIV-1 infected monocyte-derived macrophages (MDM) induced the upregulation of over 200 HBMEC proteins. These included metabolic, voltage-gated ion channels, heat shock, transport, cytoskeletal, regulatory, and calcium binding proteins. Results were validated by Western blot analysis. We conclude that HIV-1-infected MDM affect the HBMEC proteome and, in this way, affect BBB dysfunction and the development of HIV-1 CNS disease.
Ricardo-Dukelow
Mary
M
Center for Neurovirology and Neurodegenerative Disorders, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5215, USA.
Kadiu
Irena
I
Rozek
Wojciech
W
Schlautman
Joshua
J
Persidsky
Yuri
Y
Ciborowski
Pawel
P
Kanmogne
Georgette D
GD
Gendelman
Howard E
HE
D015526:AIDS Dementia Complex / Q000503:physiopathology*; D001812:Blood-Brain Barrier / Q000502:physiology* / Q000821:virology; D015153:Blotting, Western; D001921:Brain / Q000821:virology; D002478:Cells, Cultured; D018920:Coculture Techniques; D015180:Electrophoresis, Gel, Two-Dimensional; D042783:Endothelial Cells / Q000502:physiology*; D015870:Gene Expression; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000503:physiopathology*; D015497:HIV-1; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008264:Macrophages / Q000821:virology*; D040901:Proteomics; D053719:Tandem Mass Spectrometry