Department of Microbiology and Immunology, and Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
Brain Res. 2011 Jul 5;1399:96-115. doi: 10.1016/j.brainres.2011.05.015. Epub 2011 May 14.
Human immunodeficiency virus type 1 (HIV-1) primarily infects CD4(+) T cells and cells of the monocyte-macrophage lineage, resulting in immunodeficiency in an infected patient. Along with this immune deficiency, HIV-1 has been linked to a number of neurological symptoms in the absence of opportunistic infections or other co-morbidities, suggesting that HIV-1 is able to cross the blood-brain barrier (BBB), enter the central nervous system (CNS), and cause neurocognitive impairment. HIV-1-infected monocyte-macrophages traverse the BBB and enter the CNS throughout the course of HIV-1 disease. Once in the brain, both free virus and virus-infected cells are able to infect neighboring resident microglia and astrocytes and possibly other cell types. HIV-1-infected cells in both the periphery and the CNS give rise to elevated levels of viral proteins, including gp120, Tat, and Nef, and of host inflammatory mediators such as cytokines and chemokines. It has been shown that the viral proteins may act alone or in concert with host cytokines and chemokines, affecting the integrity of the BBB. The pathological end point of these interactions may facilitate a positive feedback loop resulting in increased penetration of HIV into the CNS. It is proposed in this review that the dysregulation of the BBB during and after neuroinvasion is a critical component of the neuropathogenic process and that dysregulation of this protective barrier is caused by a combination of viral and host factors including secreted viral proteins, components of the inflammatory process, the aging process, therapeutics, and drug or alcohol abuse.
人类免疫缺陷病毒 1 型（HIV-1）主要感染 CD4(+)T 细胞和单核巨噬细胞谱系的细胞，导致感染患者免疫缺陷。除了这种免疫缺陷，HIV-1 还与许多没有机会性感染或其他合并症的神经系统症状有关，这表明 HIV-1 能够穿过血脑屏障（BBB），进入中枢神经系统（CNS），并导致神经认知障碍。HIV-1 感染的单核巨噬细胞在 HIV-1 疾病的整个过程中穿过 BBB 并进入 CNS。一旦进入大脑，游离病毒和受感染的细胞都能够感染邻近的常驻小胶质细胞和星形胶质细胞，可能还有其他细胞类型。外周和中枢神经系统中的 HIV-1 感染细胞会导致病毒蛋白（包括 gp120、Tat 和 Nef）和宿主炎症介质（如细胞因子和趋化因子）的水平升高。已经表明，病毒蛋白可能单独或与宿主细胞因子和趋化因子协同作用，影响 BBB 的完整性。这些相互作用的病理终点可能促进 HIV 进入中枢神经系统的渗透增加的正反馈循环。在这篇综述中提出，在神经入侵期间和之后 BBB 的失调是神经发病过程的一个关键组成部分，这种保护性屏障的失调是由病毒和宿主因素的组合引起的，包括分泌的病毒蛋白、炎症过程的成分、衰老过程、治疗方法以及药物或酒精滥用。
