Blood-brain barrier pericytes as a target for HIV-1 infection
Blood-brain barrier pericytes as a target for HIV-1 infection
复制标题
DOI：
10.1093/brain/awy339
复制
发表时间：
2019-03-01
期刊：
影响因子：
14.5
通讯作者：
Toborek, Michal
中科院分区：
文献类型：
--
作者：
Bertrand, Luc;Cho, Hyung Joon;Toborek, Michal
周细胞是通过沿内皮近腔表面延伸的细胞质突起包裹内皮细胞的多功能细胞。血脑屏障的内皮细胞和周细胞之间的相互作用对于血脑屏障的正常形成、发育、稳定和维持是必要的。血脑屏障周细胞调节细胞间的细胞旁流动、跨内皮液体运输，维持周围微环境的最佳化学成分，并保护内皮细胞免受潜在有害物质的侵害。因此，血脑屏障周细胞的功能障碍或丧失是与微血管不稳定相关的几种疾病发病机制的重要因素。重要的是，最近的研究表明，血脑屏障周细胞可能是 HIV-1 感染的目标，能够支持有效的 HIV-1 复制。此外，血脑屏障周细胞容易产生潜伏感染，可以通过组蛋白脱乙酰酶抑制剂与 TNF 的混合物重新激活潜伏感染。血脑屏障周细胞的 HIV-1 感染已在 HIV-1 感染小鼠模型和人类 HIV-1 感染大脑死后样本中得到证实。总体而言，最近的证据表明，血脑屏障周细胞可能是大脑中以前未被识别的 HIV-1 靶点和储存库。
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.