Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY, 10461, USA.
J Leukoc Biol. 2012 Mar;91(3):401-15. doi: 10.1189/jlb.0811394. Epub 2012 Jan 6.
HIV continues to be a global health crisis with more than 34 million people infected worldwide (UNAIDS: Report on the Global AIDS Epidemic 2010, Geneva, World Health Organization). HIV enters the CNS within 2 weeks of infection and establishes a spectrum of HAND in a large percentage of infected individuals. These neurologic deficits greatly impact the quality of life of those infected with HIV. The establishment of HAND is largely attributed to monocyte transmigration, particularly that of a mature CD14(+)CD16(+) monocyte population, which is more susceptible to HIV infection, across the BBB into the CNS parenchyma in response to chemotactic signals. To enter the CNS, junctional proteins on the monocytes must participate in homo- and heterotypic interactions with those present on BMVECs of the BBB as they transmigrate across the barrier. This transmigration is responsible for bringing virus into the brain and establishing chronic neuroinflammation. While there is baseline trafficking of monocytes into the CNS, the increased chemotactic signals present during HIV infection of the brain promote exuberant monocyte transmigration into the CNS. This review will discuss the mechanisms of monocyte differentiation/maturation, HIV infectivity, and transmigration into the CNS parenchyma that contribute to the establishment of cognitive impairment in HIV-infected individuals. It will focus on markers of monocyte subpopulations, how differentiation/maturation alters HIV infectivity, and the mechanisms that promote their increased transmigration across the BBB into the CNS.
HIV 仍然是一个全球性的健康危机，全球有超过 3400 万人感染（UNAIDS：2010 年全球艾滋病流行报告，日内瓦，世界卫生组织）。HIV 在感染后 2 周内进入 CNS，并在很大比例的感染个体中建立了一系列 HAND。这些神经缺陷极大地影响了感染 HIV 人群的生活质量。HAND 的建立主要归因于单核细胞的迁移，特别是成熟的 CD14(+)CD16(+)单核细胞群体的迁移，它们更容易受到 HIV 的感染，通过趋化信号穿过 BBB 进入 CNS 实质。为了进入 CNS，单核细胞上的连接蛋白必须参与同型和异型相互作用，与 BBB 上的 BMVEC 上的连接蛋白相互作用，因为它们穿过屏障迁移。这种迁移负责将病毒带入大脑并建立慢性神经炎症。虽然单核细胞有进入 CNS 的基础迁移，但在 HIV 感染大脑期间存在的增加的趋化信号促进了单核细胞过度迁移进入 CNS。这篇综述将讨论单核细胞分化/成熟、HIV 感染性和向 CNS 实质迁移的机制，这些机制导致 HIV 感染者认知障碍的建立。它将重点讨论单核细胞亚群的标志物、分化/成熟如何改变 HIV 感染性以及促进它们穿过 BBB 向 CNS 过度迁移的机制。
