Mallard Jaclyn, Williams Kenneth C
Department of Biology, Boston College, Chestnut Hill, MA, United States.
Department of Biology, Boston College, Chestnut Hill, MA, United States.
Handb Clin Neurol. 2018;152:41-53. doi: 10.1016/B978-0-444-63849-6.00004-9.
It is difficult to study the pathogenesis of human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) in living patients because central nervous system (CNS) tissues are only available post mortem. Rodent and nonhuman primate (NHP) models of HAND allow for longitudinal analysis of HIV-associated CNS pathology and efficacy studies of novel therapeutics. Rodent models of HAND allow for studies with large sample sizes, short duration, and relatively low cost. These models include humanized mice used to study HIV-associated neuropathogenesis and transgenic mice used to study neurotoxic effects of viral proteins without infection. Simian immunodeficiency virus (SIV)-infected NHP are the premier model of neuroAIDS; SIV-associated CNS pathology is similar to HIV-associated CNS pathology with HAND. Additionally, the size, lifespan of NHP, and time to acquired immune deficiency syndrome (AIDS) progression make SIV-infected NHP models optimal for studies of viral latency and reservoirs, and assessing novel therapeutics for neuroAIDS. NHP models of neuroAIDS generally include conventional progressors (AIDS within 2-3 years) and those that have rapid disease (AIDS within 150 days). Rapid AIDS models are achieved by immune modulation and/or infection with neurovirulent and neurosuppressive viral strains and result in a high incidence of SIV-associated encephalitis. In this chapter, we briefly review rodent and NHP models of neuroAIDS, including contributions made using these models to our understanding of HIV-associated CNS disease.
由于中枢神经系统（CNS）组织只能在患者死后获取，因此很难在活着的患者中研究人类免疫缺陷病毒（HIV）相关神经认知障碍（HAND）的发病机制。HAND的啮齿动物和非人类灵长类动物（NHP）模型可用于对HIV相关的中枢神经系统病理学进行纵向分析以及新型疗法的疗效研究。HAND的啮齿动物模型可用于大样本量、短时间且成本相对较低的研究。这些模型包括用于研究HIV相关神经发病机制的人源化小鼠以及用于研究病毒蛋白的神经毒性作用（无感染）的转基因小鼠。感染猿猴免疫缺陷病毒（SIV）的NHP是神经艾滋病的主要模型；SIV相关的中枢神经系统病理学与HAND的HIV相关中枢神经系统病理学相似。此外，NHP的体型、寿命以及获得性免疫缺陷综合征（AIDS）进展时间，使得感染SIV的NHP模型成为研究病毒潜伏和病毒库以及评估神经艾滋病新型疗法的最佳选择。神经艾滋病的NHP模型通常包括传统进展型（2 - 3年内发展为AIDS）和疾病进展迅速型（150天内发展为AIDS）。迅速发展为AIDS的模型是通过免疫调节和/或感染神经毒性和神经抑制性病毒株实现的，会导致SIV相关脑炎的高发病率。在本章中，我们简要回顾神经艾滋病的啮齿动物和NHP模型，包括使用这些模型对我们理解HIV相关中枢神经系统疾病所做的贡献。
