期刊
BRAIN
卷 142, 期 -, 页码 502-511出版社
OXFORD UNIV PRESS
DOI: 10.1093/brain/awy339
关键词
blood-brain barrier pericytes; HIV; HIV reservoirs; neuroinfection; HIV-associated neurocognitive disorder
资金
- National Institutes of Health (NIH) [HL126559, DA039576, MH098891, MH072567, DA040537, DA044579]
- American Heart Association [16POST31170002]
Pericytes are multifunctional cells wrapped around endothelial cells via cytoplasmic processes that extend along the abluminal surface of the endothelium. The interactions between endothelial cells and pericytes of the blood-brain barrier are necessary for proper formation, development, stabilization, and maintenance of the blood-brain barrier. Blood-brain barrier pericytes regulate paracellular flow between cells, transendothelial fluid transport, maintain optimal chemical composition of the surrounding micro-environment, and protect endothelial cells from potential harmful substances. Thus, dysfunction or loss of blood-brain barrier pericytes is an important factor in the pathogenesis of several diseases that are associated with microvascular instability. Importantly, recent research indicates that blood-brain barrier pericytes can be a target of HIV-1 infection able to support productive HIV-1 replication. In addition, blood-brain barrier pericytes are prone to establish a latent infection, which can be reactivated by a mixture of histone deacetylase inhibitors in combination with TNF. HIV-1 infection of blood-brain barrier pericytes has been confirmed in a mouse model of HIV-1 infection and in human post-mortem samples of HIV-1-infected brains. Overall, recent evidence indicates that blood-brain barrier pericytes can be a previously unrecognized HIV-1 target and reservoir in the brain.
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