The face of the HIV-1/AIDS pandemic has changed significantly thanks to the development of antiretroviral therapy (ART) regimens. Unfortunately, several HIV-associated comorbidities continuously occur in the clinical population, most notably HIV-associated neurocognitive disorders (HAND). While many molecular and cellular mechanisms have been characterized by describing HAND pathology (specifically neuroinflammatory insults and oxidative stress) in the ART era, compromised adult neurogenesis is emerging as a potential new mechanism. Neurogenesis is a dynamic process that generates new neurons and glial cells from neural stem cells (NSCs) and neural progenitor cells (NPCs) in specific areas of the brain. There are increasing observations that HIV-1 can productively and non-productively infect NSCs and NPCs. HIV-1 proteins and/or secondary immune/inflammatory responses impair the initial differentiation process of NSCs to NPCs, restrict neuronal lineage differentiation, and aberrantly promote astrocytic lineage differentiation. Recent studies with HIV-1 transgenic animal models demonstrate varying degrees of adult neurogenic deficits, which correlate with milder to moderate forms of neurocognitive impairments. The neurogenic dysfunction underlying HAND highlights the importance of developing potential therapeutics to restore adult neurogenic homeostasis in HIV-1 patients.

中文翻译：

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HIV-1 和受损的成人神经发生：手持久性新范式的新证据

由于抗逆转录病毒疗法 (ART) 方案的发展，HIV-1/AIDS 大流行的面貌发生了显着变化。不幸的是，临床人群中不断出现一些与 HIV 相关的合并症，最显着的是 HIV 相关的神经认知障碍 (HAND)。虽然许多分子和细胞机制的特点是在 ART 时代描述 HAND 病理学（特别是神经炎症损伤和氧化应激），但成人神经发生受损正在成为一种潜在的新机制。神经发生是一个动态过程，它从大脑特定区域的神经干细胞 (NSC) 和神经祖细胞 (NPC) 生成新的神经元和神经胶质细胞。越来越多的观察表明，HIV-1 可以有效和无效地感染 NSC 和 NPC。HIV-1 蛋白和/或继发性免疫/炎症反应会损害 NSC 向 NPC 的初始分化过程，限制神经元谱系分化，并异常促进星形细胞谱系分化。最近对 HIV-1 转基因动物模型的研究表明，不同程度的成人神经源性缺陷与轻度至中度形式的神经认知障碍相关。HAND 背后的神经源性功能障碍突出了开发潜在疗法以恢复 HIV-1 患者成人神经源性稳态的重要性。最近对 HIV-1 转基因动物模型的研究表明，不同程度的成人神经源性缺陷与轻度至中度形式的神经认知障碍相关。HAND 背后的神经源性功能障碍突出了开发潜在疗法以恢复 HIV-1 患者成人神经源性稳态的重要性。最近对 HIV-1 转基因动物模型的研究表明，不同程度的成人神经源性缺陷与轻度至中度形式的神经认知障碍相关。HAND 背后的神经源性功能障碍突出了开发潜在疗法以恢复 HIV-1 患者成人神经源性稳态的重要性。