Brain tissue transcriptomic analysis of SIV-infected macaques identifies several altered metabolic pathways linked to neuropathogenesis and poly (ADP-ribose) polymerases (PARPs) as potential therapeutic targets.
Brain tissue transcriptomic analysis of SIV-infected macaques identifies several altered metabolic pathways linked to neuropathogenesis and poly (ADP-ribose) polymerases (PARPs) as potential therapeutic targets.
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SIV感染猕猴的脑组织转录组学分析确定了与神经发病机制和聚（ADP-核糖）聚合酶（PARP）相关的几种改变的代谢途径作为潜在的治疗靶点。
DOI：
10.1007/s13365-020-00927-z
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发表时间：
2021-03
影响因子：
3.2
通讯作者：
Salemi M
中科院分区：
文献类型：
--
作者：
Mavian C;Ramirez-Mata AS;Dollar JJ;Nolan DJ;Cash M;White K;Rich SN;Magalis BR;Marini S;Prosperi MCF;Amador DM;Riva A;Williams KC;Salemi M
尽管抗逆转录病毒治疗有所改善，但人类免疫缺陷病毒1型（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。手显着影响个人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不断增加，但尚未确定明确的诊断或预后标志物。我们研究了在不同感染阶段处死的猴免疫缺陷病毒（SIV）感染恒河猴的额叶皮质组织中的转录组学特征。基于额叶皮质组织中病毒的可检测（n = 6）或不可检测（n = 5）存在，在SIV感染的动物（n = 11）中比较了有或没有CD 8+淋巴细胞耗竭的基因表达。在可检测到脑感染的动物中发现单核细胞和巨噬细胞细胞途径活化的显著富集，与CD 8+淋巴细胞耗竭无关。此外，四聚（ADP-核糖）聚合酶（PARP）的转录上调额叶皮层，这是证实了实时聚合酶链反应。我们的研究结果揭示了PARP参与SIV感染大脑及其在SIV相关神经退行性过程中的作用。抑制PARP可能为HIV相关神经病理学提供有效的新治疗靶点。
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.
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影响因子：
7.4
作者：
Gill, Roop;Tsung, Allan;Billiar, Timothy
通讯作者：
Billiar, Timothy
影响因子：
5.3
作者：
Gianella, Sara;Pond, Sergei L. Kosakovsky;Ellis, Ronald J.
通讯作者：
Ellis, Ronald J.
影响因子：
4.4
作者：
Caprara, Greta;Prosperini, Elena;Natoli, Gioacchino
通讯作者：
Natoli, Gioacchino
影响因子：
3.5
作者：
Das BC;Thapa P;Karki R;Das S;Mahapatra S;Liu TC;Torregroza I;Wallace DP;Kambhampati S;Van Veldhuizen P;Verma A;Ray SK;Evans T
通讯作者：
Evans T
影响因子：
12.3
作者：
Conesa A;Madrigal P;Tarazona S;Gomez-Cabrero D;Cervera A;McPherson A;Szcześniak MW;Gaffney DJ;Elo LL;Zhang X;Mortazavi A
通讯作者：
Mortazavi A