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. 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. 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.

尽管抗逆转录病毒疗法有所改进，但 1 型人类免疫缺陷病毒 (HIV-1) 相关的神经认知障碍 (HAND) 在接受治疗的受试者中仍然普遍存在。HAND 显着影响个体的生活质量以及对治疗的依从性，尽管对神经发病机制的了解越来越多，但尚未确定明确的诊断或预后标志物。我们调查了在感染的不同阶段处死的猴免疫缺陷病毒 (SIV) 感染的恒河猴额叶皮层组织的转录组学特征。基因表达SIV感染的动物（间比较Ñ  = 11），有或没有CD8 +淋巴细胞耗竭，基于检测的（Ñ  = 6）或不可检测（Ñ = 5) 额叶皮层组织中存在病毒。在可检测到脑部感染的动物中发现单核细胞和巨噬细胞通路的激活显着富集，与 CD8+ 淋巴细胞耗竭无关。此外，四种多聚（ADP-核糖）聚合酶（PARP）的转录在额叶皮层中上调，实时聚合酶链反应证实了这一点。我们的结果阐明了 PARP 参与 SIV 大脑感染及其在 SIV 相关神经退行性过程中的作用。抑制 PARPs 可能为 HIV 相关神经病理学提供有效的新治疗靶点。