TY - JOUR
T1 - Blood-brain barrier pericytes as a target for HIV-1 infection
AU - Bertrand, Luc
AU - Cho, Hyung Joon
AU - Toborek, Michal
N1 - Funding Information:
Supported by the National Institutes of Health (NIH), grants HL126559, DA039576, MH098891, MH072567, DA040537, and DA044579. L.B. was supported in part by a postdoctoral fellowship from the American Heart Association (16POST31170002).
Publisher Copyright:
© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - 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.
AB - 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.
KW - HIV
KW - HIV reservoirs
KW - HIV-associated neurocognitive disorder
KW - blood-brain barrier pericytes
KW - neuroinfection
UR - http://www.scopus.com/inward/record.url?scp=85062499320&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062499320&partnerID=8YFLogxK
U2 - 10.1093/brain/awy339
DO - 10.1093/brain/awy339
M3 - Article
C2 - 30668645
AN - SCOPUS:85062499320
VL - 142
SP - 502
EP - 511
JO - Brain
JF - Brain
SN - 0006-8950
IS - 3
ER -