Central nervous system (CNS) transcriptomic correlates of human immunodeficiency virus (HIV) brain RNA load in HIV-infected individuals.
Central nervous system (CNS) transcriptomic correlates of human immunodeficiency virus (HIV) brain RNA load in HIV-infected individuals.
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DOI：
10.1038/s41598-021-88052-7
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发表时间：
2021-06-09
影响因子：
4.6
通讯作者：
Repunte-Canonigo V
中科院分区：
文献类型：
--
作者：
Sanna PP;Fu Y;Masliah E;Lefebvre C;Repunte-Canonigo V
To generate new mechanistic hypotheses on the pathogenesis and disease progression of neuroHIV and identify novel therapeutic targets to improve neuropsychological function in people with HIV, we investigated host genes and pathway dysregulations associated with brain HIV RNA load in gene expression profiles of the frontal cortex, basal ganglia, and white matter of HIV+ patients. Pathway analyses showed that host genes correlated with HIV expression in all three brain regions were predominantly related to inflammation, neurodegeneration, and bioenergetics. HIV RNA load directly correlated particularly with inflammation genesets representative of cytokine signaling, and this was more prominent in white matter and the basal ganglia. Increases in interferon signaling were correlated with high brain HIV RNA load in the basal ganglia and the white matter although not in the frontal cortex. Brain HIV RNA load was inversely correlated with genesets that are indicative of neuronal and synaptic genes, particularly in the cortex, indicative of synaptic injury and neurodegeneration. Brain HIV RNA load was inversely correlated with genesets that are representative of oxidative phosphorylation, electron transfer, and the tricarboxylic acid cycle in all three brain regions. Mitochondrial dysfunction has been implicated in the toxicity of some antiretrovirals, and these results indicate that mitochondrial dysfunction is also associated with productive HIV infection. Genes and pathways correlated with brain HIV RNA load suggest potential therapeutic targets to ameliorate neuropsychological functioning in people living with HIV.
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DOI：
10.1136/bmj.c3666
发表时间：
2010-07-26
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Debette S;Markus HS
通讯作者：
Markus HS
DOI：
10.1097/qai.0000000000000532
发表时间：
2015-05-01
期刊：
Journal of acquired immune deficiency syndromes (1999)
影响因子：
--
作者：
Anderson AM;Harezlak J;Bharti A;Mi D;Taylor MJ;Daar ES;Schifitto G;Zhong J;Alger JR;Brown MS;Singer EJ;Campbell TB;McMahon DD;Buchthal S;Cohen R;Yiannoutsos C;Letendre SL;Navia BA;HIV Neuroimaging Consortium
通讯作者：
HIV Neuroimaging Consortium
影响因子：
11.2
作者：
Brierley, EJ;Johnson, MA;Turnbull, DM
通讯作者：
Turnbull, DM
影响因子：
3.8
作者：
Dahl, Viktor;Peterson, Julia;Price, Richard W.
通讯作者：
Price, Richard W.
影响因子：
3.2
作者：
Daily, Abigail;Nath, Avindra;Hersh, Louis B.
通讯作者：
Hersh, Louis B.