Department of Microbiology and Immunology, Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.
Adv Virus Res. 2013;87:183-240. doi: 10.1016/B978-0-12-407698-3.00006-5.
HIV-associated neurologic disease continues to be a significant complication in the era of highly active antiretroviral therapy. A substantial subset of the HIV-infected population shows impaired neuropsychological performance as a result of HIV-mediated neuroinflammation and eventual central nervous system (CNS) injury. CNS compartmentalization of HIV, coupled with the evolution of genetically isolated populations in the CNS, is responsible for poor prognosis in patients with AIDS, warranting further investigation and possible additions to the current therapeutic strategy. This chapter reviews key advances in the field of neuropathogenesis and studies that have highlighted how molecular diversity within the HIV genome may impact HIV-associated neurologic disease. We also discuss the possible functional implications of genetic variation within the viral promoter and possibly other regions of the viral genome, especially in the cells of monocyte-macrophage lineage, which are arguably key cellular players in HIV-associated CNS disease.
HIV 相关的神经疾病在高效抗逆转录病毒治疗时代仍然是一个重要的并发症。相当一部分 HIV 感染者由于 HIV 介导的神经炎症和最终的中枢神经系统(CNS)损伤,表现出神经认知功能障碍。HIV 在中枢神经系统的分隔,加上中枢神经系统中遗传上隔离的群体的演变,导致 AIDS 患者预后不良,需要进一步研究,并可能对当前的治疗策略进行补充。本章回顾了神经发病机制领域的重要进展,并强调了 HIV 基因组内的分子多样性如何影响 HIV 相关的神经疾病。我们还讨论了病毒启动子和可能其他病毒基因组区域内遗传变异的可能功能意义,特别是在单核细胞-巨噬细胞谱系的细胞中,这些细胞可以说是 HIV 相关的中枢神经系统疾病的关键细胞。