Infection of human pericytes by HIV-1 disrupts the integrity of the blood-brain barrier.

Infection of human pericytes by HIV-1 disrupts the integrity of the blood-brain barrier.
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DOI:
10.1111/j.1582-4934.2012.01622.x
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发表时间:
2012-12
影响因子:
5.3
通讯作者:
Toborek M
Toborek M
中科院分区:
医学2区
文献类型:
--
作者:
Nakagawa S;Castro V;Toborek M

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人类免疫缺陷病毒1型(HIV-1)感染中枢神经系统(CNS)会影响神经血管单元的单个细胞类型之间的串扰,从而导致血脑屏障(BBB)的破坏和神经功能障碍的发展。尽管HIV-1对神经元、星形胶质细胞和脑内皮细胞的毒性已被广泛研究,但尚未有关于HIV-1对周细胞影响的报道。因此,本研究的目的是评估周细胞是否可以感染HIV-1,以及这种感染如何影响脑内皮细胞的屏障功能。我们的研究结果表明,人脑周细胞表达HIV-1主要受体CD4和副受体CXCR4和CCR5。我们还通过HIV-1 p24 ELISA检测,确定HIV-1可以在人脑周细胞中复制,尽管水平较低。周细胞对嗜x4型NL4-3和嗜r5型JR-CSF HIV-1株均敏感。此外,周细胞的HIV-1感染导致血脑屏障体外模型的完整性受损。这些发现表明,人类大脑周细胞可以被HIV-1感染,并提示感染的周细胞参与了HIV-1诱导的中枢神经系统损伤的进展。
Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) affects cross-talk between the individual cell types of the neurovascular unit, which then contributes to disruption of the blood–brain barrier (BBB) and the development of neurological dysfunctions. Although the toxicity of HIV-1 on neurons, astrocytes and brain endothelial cells has been widely studied, there are no reports addressing the influence of HIV-1 on pericytes. Therefore, the purpose of this study was to evaluate whether or not pericytes can be infected with HIV-1 and how such an infection affects the barrier function of brain endothelial cells. Our results indicate that human brain pericytes express the major HIV-1 receptor CD4 and co-receptors CXCR4 and CCR5. We also determined that HIV-1 can replicate, although at a low level, in human brain pericytes as detected by HIV-1 p24 ELISA. Pericytes were susceptible to infection with both the X4-tropic NL4-3 and R5-tropic JR-CSF HIV-1 strains. Moreover, HIV-1 infection of pericytes resulted in compromised integrity of an in vitro model of the BBB. These findings indicate that human brain pericytes can be infected with HIV-1 and suggest that infected pericytes are involved in the progression of HIV-1-induced CNS damage.
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