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| Status |
Public on Feb 28, 2023 |
| Title |
MicroRNA profiling of Basal ganglia tissue from chronically SIV infected rhesus macaques II |
| Platform organism |
Homo sapiens |
| Sample organism |
Macaca mulatta |
| Experiment type |
Expression profiling by RT-PCR
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| Summary |
The study describes miRNA expression changes in basal ganglia (BG) of chronically SIV-infected rhesus macaques. HIV/SIV-associated neurological disorder (HAND) represents a major comorbidity affecting HIV patients on anti-retroviral therapy. Employing a systems biology approach, we report molecular changes underlying HAND and its modulation by phytocannabinoids [delta-9-tetrahydrocannabinol (9-THC)] in uninfected and SIV-infected rhesus macaques (RMs) treated with vehicle (VEH/SIV) or 9-THC (THC/SIV). VEH/SIV but not THC/SIV RMs showed significant enrichment of genes linked to anti-viral defense, interferon-beta, NFkB, RIG-1, and JAK-STAT signaling. We focused on the anti-endoplasmic reticulum (WFS1) and anti-oxidative stress (CRYM) proteins that were significantly downregulated in BG of VEH/SIV RMs. Both proteins localized to the BG neurons, and showed differential expression in the BG of THC/SIV and VEH/SIV RMs. Additionally, inflammation-associated miR-155 and miR-142-3p showed significantly higher expression in the BG of VEH/SIV RMs. In human primary HCN2 neuronal cells, miR-142-3p post-transcriptionally downregulated WFS1. These findings strongly support a role for differential miRNA expression associated with HIV/SIV induced neurological dysfunction.
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| Overall design |
Fourteen age and weight matched adult Indian rhesus macaques were randomly divided into 3 groups. Group 1 (n=4) remained uninfected. Group 2 (VEH/SIV, n=4) animals were treated with vehicle and infected intravenously with 100TCID50 of SIVmac251. Group 3 (THC/SIV, n=6) were treated with delta-9-tetrahydrocannabinol and infected intravenously with 100TCID50 SIVmac251. Basal ganglia tissue was collected at necropsy. ~100 ng of total RNA was first reverse transcribed and preamplified according to the manufacturer’s recommendation. MicroRNA expression profiling was performed using TaqMan ®OpenArray® Human microRNA panels. Data analysis was performed using Omics Office StatMiner qPCR analysis software, TIBCO Spotfire, (Perkin Elmer, Waltham, MA), which utilizes the comparative Cτ (ΔΔCτ) method to rapidly and accurately quantify relative miRNA expression across many genes and samples. miRNA expression data were normalized using the global normalization method. Comparisons were made between uninfected and VEH/SIV and THC/SIV and VEH/SIV rhesus macaques.
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| Contributor(s) |
Mohan M |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Dec 12, 2022 |
| Last update date |
Feb 28, 2023 |
| Contact name |
Mahesh Mohan |
| E-mail(s) |
mmohan@txbiomed.org
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| Organization name |
Southwest National Primate Research Center
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| Department |
Host Pathogen Interaction Program
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| Lab |
12/106
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| Street address |
8715 West Military Road
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| City |
San Antonio |
| State/province |
Texas |
| ZIP/Postal code |
78227 |
| Country |
USA |
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| Platforms (1) |
| GPL17837 |
TaqMan OpenArray Human MicroRNA Panel (4461104) |
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| Samples (14)
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| This SubSeries is part of SuperSeries: |
| GSE220783 |
Cannabinoid modulation of gene and microRNA expression in brain (basal ganglia) during chronic HIV/SIV infection |
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| Relations |
| BioProject |
PRJNA911219 |
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