Molecular Neuroscience and Vascular Biology Laboratory, Department of Neurosurgery, University of Kentucky Medical Center, Lexington, KY, USA.
J Cell Mol Med. 2012 Dec;16(12):2950-7. doi: 10.1111/j.1582-4934.2012.01622.x.
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.
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中各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，但尚无关于 HIV-1 对周细胞影响的报道。因此，本研究旨在评估周细胞是否可能被 HIV-1 感染，以及这种感染如何影响脑内皮细胞的屏障功能。我们的结果表明，人脑周细胞表达主要的 HIV-1 受体 CD4 以及辅助受体 CXCR4 和 CCR5。我们还确定 HIV-1 可以在人脑周细胞中复制，尽管水平较低，可通过 HIV-1 p24 ELISA 检测到。周细胞易受 X4 嗜性 NL4-3 和 R5 嗜性 JR-CSF HIV-1 株的感染。此外，HIV-1 感染周细胞会导致体外 BBB 模型的完整性受损。这些发现表明人脑周细胞可能被 HIV-1 感染，并提示受感染的周细胞参与了 HIV-1 诱导的 CNS 损伤的进展。
