Blood-brain barrier pericytes as a target for HIV-1 infection.

TitleBlood-brain barrier pericytes as a target for HIV-1 infection.
Publication TypeJournal Article
Year of Publication2019
AuthorsBertrand, L, Cho, HJoon, Toborek, M
JournalBrain
Volume142
Issue3
Pagination502-511
Date Published2019 03 01
ISSN1460-2156
KeywordsAnimals, Biological Transport, Blood-Brain Barrier, Brain, Endothelial Cells, HIV Infections, HIV-1, Humans, Mice, Pericytes
Abstract

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 microenvironment, 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.

DOI10.1093/brain/awy339
Alternate JournalBrain
PubMed ID30668645
PubMed Central IDPMC6391611
Grant ListR01 MH063022 / MH / NIMH NIH HHS / United States
R01 DA044579 / DA / NIDA NIH HHS / United States
R01 DA027569 / DA / NIDA NIH HHS / United States
R01 HL126559 / HL / NHLBI NIH HHS / United States
R01 NS039254 / NS / NINDS NIH HHS / United States
R01 DA039576 / DA / NIDA NIH HHS / United States
R01 DA040537 / DA / NIDA NIH HHS / United States
R01 MH098891 / MH / NIMH NIH HHS / United States
R01 MH072567 / MH / NIMH NIH HHS / United States