Background: Despite improvements in antiretroviral therapy, human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders (HAND) remain prevalent in subjects undergoing therapy. HAND significantly affects individuals quality of life, as well as adherence to therapy, and, despite the increasing understanding of neuropathogenesis, no definitive diagnostic or prognostic marker has been identified. Results: We investigated transcriptomic profiles in frontal cortex tissues of Simian immunodeficiency virus (SIV)-infected Rhesus macaques sacrificed at different stages of infection. Gene expression was compared among SIV-infected animals (n=11), with or without CD8+ lymphocyte depletion, based on detectable (n=6) or non-detectable (n=5) presence of the virus in frontal cortex tissues. Significant enrichment in activation of monocyte and macrophage cellular pathways was found in animals with detectable brain infection, independently from CD8+ lymphocyte depletion. In addition, transcripts of four poly (ADP-ribose) polymerases (PARPs) were up-regulated in the frontal cortex, which was confirmed by real-time polymerase chain reaction. Conclusions: Our results shed light on involvement of PARPs in SIV infection of the brain and their role in SIV-associated neurodegenerative processes. Inhibition of PARPs may provide an effective novel therapeutic target for HIV-related neuropathology.

中文翻译：

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对SIV感染猕猴的脑组织转录组学分析确定了与神经病发病相关的几种改变的代谢途径，而聚（ADP-核糖）聚合酶（PARP）是潜在的治疗靶标

背景：尽管抗逆转录病毒疗法有所改善，但人类1型免疫缺陷病毒（HIV-1）相关的神经认知障碍（HAND）在接受治疗的受试者中仍很普遍。HAND会显着影响个体的生活质量以及对治疗的依从性，尽管对神经病的认识日益加深，但仍未确定明确的诊断或预后标志物。结果：我们调查了在感染的不同阶段处死的猿猴免疫缺陷病毒（SIV）感染的恒河猴的额叶皮层组织中的转录组谱。根据额叶皮层组织中可检测到的病毒（n = 6）或不可检测到的病毒（n = 5）的存在，比较是否感染了SIV的动物（n = 11）中有无CD8 +淋巴细胞的基因表达。在可检测到的脑部感染的动物中，发现单核细胞和巨噬细胞细胞途径的激活显着富集，而与CD8 +淋巴细胞耗竭无关。另外，额叶皮层中四种聚（ADP-核糖）聚合酶（PARP）的转录物上调，这通过实时聚合酶链反应得以证实。结论：我们的结果揭示了PARPs参与脑SIV感染及其在SIV相关神经退行性过程中的作用。抑制PARPs可能为HIV相关的神经病理学提供有效的新型治疗靶标。实时聚合酶链反应证实了这一点。结论：我们的结果揭示了PARPs参与脑SIV感染及其在SIV相关神经退行性过程中的作用。抑制PARPs可能为HIV相关的神经病理学提供有效的新型治疗靶标。实时聚合酶链反应证实了这一点。结论：我们的结果揭示了PARPs参与脑SIV感染及其在SIV相关神经退行性过程中的作用。抑制PARPs可能为HIV相关的神经病理学提供有效的新型治疗靶标。