Central nervous system (CNS) transcriptomic correlates of human immunodeficiency virus (HIV) brain RNA load in HIV-infected individuals
Autor: | Vez Repunte-Canonigo, Yu Fu, Pietro Paolo Sanna, Celine Lefebvre, Eliezer Masliah |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Male
0301 basic medicine Science Central nervous system HIV Infections Biology Neural circuits Article Transcriptome 03 medical and health sciences 0302 clinical medicine Central Nervous System Diseases Interferon Basal ganglia Gene expression medicine Animals Humans Rats Wistar Gene Multidisciplinary Neurodegeneration Brain RNA Viral Load medicine.disease United States Rats 030104 developmental biology medicine.anatomical_structure Immunology HIV-1 RNA Viral Diseases of the nervous system Medicine Rats Transgenic 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-14 (2021) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | 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. |
Databáze: | OpenAIRE |
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