Evolving paradigms in the pathogenesis of HIV-1-associated dementia
Evolving paradigms in the pathogenesis of HIV-1-associated dementia
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DOI：
10.1017/s1462399405010239
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发表时间：
2005-12-02
影响因子：
6.2
通讯作者：
Rappaport, Jay
中科院分区：
文献类型：
--
作者：
Fischer-Smith, Tracy;Rappaport, Jay
HIV-1相关性痴呆（HIV-D）仍然是HIV-1感染和AIDS的重要后果。自从临床上采用高效抗逆转录病毒疗法以来，艾滋病毒-D的发病率有所下降，但随着患者接受治疗的寿命延长，患病率有所上升。此外，一种不太严重的HIV-D形式，即轻微的认知运动障碍，已成为一个日益严重的问题。已经提出了两种不同的模型用于HIV-D中病毒进入中枢神经系统（CNS）。在“特洛伊木马”模型中，病毒早期由巨噬细胞携带进入CNS并感染驻留的神经胶质细胞;在感染过程后期，病毒复制被激活，额外的单核细胞/巨噬细胞通过细胞因子/趋化因子网络和血脑屏障处的内皮细胞-白细胞相互作用被募集到CNS中。在“晚期侵袭”模型中，由于AIDS背景下外周免疫失调，固有侵袭性活化单核细胞亚群从骨髓中扩增。在这篇综述中，我们讨论了这两个独立的，虽然不是相互排斥的，病毒进入和持久性在中枢神经系统的手段。此外，我们探索神经元损伤和凋亡的机制，包括病毒，病毒和宿主蛋白，氧化应激和感染或未感染的活化小胶质细胞和星形胶质细胞的产物的作用。潜在的治疗策略也进行了简要讨论。
HIV-1-associated dementia (HIV-D) remains a significant consequence of HIV-1 infection and AIDS. Since the clinical introduction of highly active antiretroviral therapy (HAART), the incidence of HIV-D has decreased, yet the prevalence has increased as patients are living longer under treatment. Additionally, a less severe form of HIV-D, minor cognitive motor disorder, has become an increasing issue. Two different models have been proposed for virus entry in the central nervous system (CNS) in HIV-D. In the 'Trojan horse' model, the virus enters the CNS early carried by macrophages and infects resident glia; later in the course of infection, virus replication is activated and additional monocyte/macrophages are recruited into the CNS via cytokine/chemokine networks and endothelial-cell-leukocyte interactions at the blood-brain barrier. In the 'late invasion' model, an inherently invasive activated monocyte subset is expanded from bone marrow as a result of immune dysregulation in the periphery in the setting of AIDS. In this review we discuss these two separate, although not mutually exclusive, means for virus entry and persistence in the CNS. Additionally, we explore mechanisms for neuronal injury and apoptosis, including the role of virus, viral and host proteins, oxidative stress and products of infected or uninfected activated microglia and astrocytes. Potential therapeutic strategies are also briefly discussed.