Single nuclei transcriptome profiling in addiction circuitry of the HIV+ brain

HIV相关神经认知障碍(HAND)坚持联合抗逆转录病毒时代 治疗(购物车)。HIV潜伏期和HIV转录本在人中枢神经系统中的细胞特异性表达 不完全了解，尽管艾滋病毒相关神经疾病的发病率仍然很高， 使用CART稳定抑制的患者对中枢神经系统病毒逃逸的认知度增加。关于CNS的问题 功能缺陷因阿片剂和其他物质使用的共同登记流行而进一步复杂化 艾滋病毒/艾滋病患者的疾病(PLWHA)，因为SUD对中枢神经系统也有深远的影响 功能，并可能对艾滋病毒的潜伏期。在中枢神经系统中，这一点在神经解剖学中表现得最为明显 HIV和SUD在纹状体黑质多巴胺能回路及其皮质投射区域的重叠 前扣带回皮质，功能性和神经生物学疾病的好发部位，以及 艾滋病毒感染的负担增加。因此，直接利用这些区域的脑组织，从 神经学特征良好的HIV感染者，有无SUD，这项申请的目标是 将探索艾滋病毒信号转录本中的多巴胺能回路是否存在于L体内 在过去几年中，S与前瞻性监测的神经状态有关 (3)探索艾滋病毒在大脑潜在储藏细胞中的表达， 包括小胶质细胞。这里提出的创新实验有望为 特定脑细胞的转录图谱和探索神经基因组状态之间的潜在联系 感染的大脑、神经和认知症状以及药物滥用。在认识到 在高风险方面，这些分析仍将在以下方面具有可预测的高收益 了解PLWHA和SUD中HIV相关中枢神经系统疾病潜在的复杂神经生物学。

HIV-associated neurocognitive disorders (HAND) persist in the era of combination antiretroviral therapy (cART). HIV latency, and cell-specific expression of HIV transcript in human CNS remains incompletely understood, despite continued high prevalence of HIV-associated neurologic disease and increasing recognition of CNS viral escape in people stably suppressed with cART. Issues of CNS functional deficit are further complicated by the co-registered epidemic of opiate and other substance use disorders (SUD) in people living with HIV/AIDS (PLWHA), as SUD also have profound impact on CNS function, and potentially on HIV latency. Nowhere in the CNS is this more evident than in the neuroanatomic overlap of HIV and SUD in striatonigral dopaminergic circuitry and its cortical projection areas including the anterior cingulate cortex, sites of predilection for functional and neurobiologic disease as well as for increased burden of HIV infection. Accordingly, directly utilizing brain tissues in these regions, from neurologically well-characterized HIV-infected individuals with and without SUD, the goal of this application will be to explore whether HIV signatures in transcriptomes in dopaminergic circuitry i n c l u d i n g c i n g u l a t e t a r g e t s is associated with prospectively monitored neurological status in the years before death and exposure to drug of abuse; (iii) explore HIV expression in potential reservoir cells of the brain, including microglia. The innovative experiments proposed here are expected to offer novel insights into transcriptomic landscapes in specific brain cells and explore potential links between neurogenomic status of the infected brain and neurological and cognitive symptoms and substance abuse. While recognizing the high-risk aspects, these analyses will nevertheless have predictable, high gain benefits in understanding the complex neurobiology underlying HIV-associated CNS disease in PLWHA and SUD.