MiRNA profiling of Macaca mulatta intact colon samples during acute SIV infection
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ABSTRACT:
ORGANISM(S): Homo sapiens Macaca mulatta
PROVIDER: GSE56624 | GEO | 2014/06/01
SECONDARY ACCESSION(S): PRJNA244150
REPOSITORIES: GEO
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Project description:This study describes differential miRNA expression in intact colon tissue during acute SIV infection of rhesus macaques. Nine miRNAs were found to be significantly affected by infection, with 5 down-regulated and 4 up-regulated miRNAs. The expression of one upregulated miRNA was further characterized and found to be significantly elevated specifically in response to SIV replication and not immune activation/inflammation accompanying SIV infection. We performed TaqMan Low Density Array based high throughput miRNA analysis on intact colon tissue from 10 acutely SIV-infected and 5 uninfected control macaques. All SIV-infected animals were inoculated intravenously with 100TCID50 of SIV. Out of the ten, one animal each was at 7, 8 and 10DPI (days post infection), 3 each at 13 and 21DPI, and 1 at 29DPI. microRNA reverse transcription and preamplification was performed according to the manufacturerM-bM-^@M-^Ys recommendation. Data analysis was performed using RQ Manager 1.2.2 and DataAssist v3.01 software. Data was normalized using Global normalization method and multiple comparisons correction was performed using Benjamini-Hochberg method.
2014-06-01 | E-GEOD-56624 | biostudies-arrayexpress
Project description:This study describes differential miRNA expression in intact colon tissue during chronic SIV infection of rhesus macaques. Ten miRNAs were found to be significantly affected by infection, with 7 down-regulated and 3 up-regulated miRNAs. The expression of one upregulated miRNA was further characterized and found to be upregulated in both colonic epithelium and lamain propria cells. Further, its expression positively correlated with colonic inflammation scores and viral loads. Additional studies suggested that its expression was driven in response to oxidative stress induced double stranded DNA damage response and may play a role in chronic activation of colonic plasma cells.
2014-12-01 | GSE60773 | GEO
Project description:The study describes miRNA expression in intact duodenum following chronic delta 9 tetrahydrocannabinol (Δ9-THC) administration to SIV-infected rhesus macaques. Chronic Δ9-THC administration to uninfected macaques significantly and positively modulated intestinal miRNA expression by increasing the total number of differentially expressed miRNAs from 14 to 60 days post infection (DPI). At 60DPI, ~28% of miRNAs showed decreased expression in VEH/SIV compared to none in the THC/SIV group. Furthermore, compared to the VEH/SIV group, THC selectively upregulated the expression of miR-10a, miR-24, miR-99b, miR-145, miR-149 and miR-187 previously shown to target proinflammatory molecules. NOX4, a potent reactive oxygen species generator was confirmed as a direct miR-99b target. A significant increase in NOX4+ crypt epithelial cells was detected in VEH/SIV compared to the THC/SIV group. We speculate that miR-99b-mediated NOX4 downregulation may protect the intestinal epithelium from oxidative stress-induced damage.
2014-11-19 | GSE61654 | GEO
Project description:The study describes miRNA expression in intact duodenum following chronic delta 9 tetrahydrocannabinol (M-NM-^T9-THC) administration to SIV-infected rhesus macaques. Chronic M-NM-^T9-THC administration to uninfected macaques significantly and positively modulated intestinal miRNA expression by increasing the total number of differentially expressed miRNAs from 14 to 60 days post infection (DPI). At 60DPI, ~28% of miRNAs showed decreased expression in VEH/SIV compared to none in the THC/SIV group. Furthermore, compared to the VEH/SIV group, THC selectively upregulated the expression of miR-10a, miR-24, miR-99b, miR-145, miR-149 and miR-187 previously shown to target proinflammatory molecules. NOX4, a potent reactive oxygen species generator was confirmed as a direct miR-99b target. A significant increase in NOX4+ crypt epithelial cells was detected in VEH/SIV compared to the THC/SIV group. We speculate that miR-99b-mediated NOX4 downregulation may protect the intestinal epithelium from oxidative stress-induced damage. Twelve age and weight matched male Indian rhesus macaques were randomly divided into 4 groups. Group 1 (n=1) received vehicle (1:1:18 of emulphor : alcohol : saline) and no infection. Group 2 (THC only, n=3) animals received twice daily intramuscular injections of M-NM-^T9-THC and no infection. Group-3 THC/SIV, (n=4) animals received twice daily injections of vehicle and were infected intravenously with 100TCID50 of SIVmac251. Group-4 (VEH/SIV, n=4) animals received twice daily injections of M-NM-^T9-THC similar to group 1 for four weeks prior to SIV infection. Duodenal pinch biopsies were collected before infection and thereafter at 14 and 30 days post infection. All animals were necropsied at 60 days post SIV infection. ~100 ng of total RNA was first reverse transcribed and preamplified according to the manufacturerM-bM-^@M-^Ys recommendation. microRNA expression profiling was performed using TaqMan M-BM-.OpenArrayM-BM-. Human microRNA panels. Data analysis was performed using ExpressionSuiteM-BM-. software. Data was normalized to three endogenous controls (RNU44, RNU48 and snoU6). Delta CT values were calculated by subtracting individual miRNA CT values from an average of all three endogenous controls. Comparisons were made between preinfection and all three treatment groups at 14, 30 and 60 DPI. To determine the effect of chronic THC treatment during SIV infection, comparisons were also made between VEH/SIV and THC/SIV at all three time points.
2014-11-19 | E-GEOD-61654 | biostudies-arrayexpress
Project description:The study describes miRNA expression in colonic epithelium of chronic SIV-infected rhesus macaques. We profiled and characterized miRNA/mRNA expression exclusively in colonic epithelium (CE) of 12 chronically SIV-infected and 8 control rhesus macaques (RMs). About 46 miRNAs were differentially expressed (DE) (20-up and 26-down) in CE during chronic SIV infection. Using TargetScan, we bioinformatically crossed the predicted targets of DE miRNAs to genome-wide transcriptomic data and identified several critical miRNA-mRNA pairings that suggested miRNA-mediated regulation of aberrant epithelial gene expression in CE. Immunofluorescence, luciferase reporter and miRNA overexpression studies confirmed the ability of miR-130a and miR-212 to bind the 3’ UTR and downregulate protein expression of occludin (OCLN) and peroxisome proliferator activator receptor gamma (PPAR), respectively, two proteins with pivotal roles in epithelial barrier function. MiR-130a and miR-212 overexpression in Caco-2 cells significantly reduced transepithelial electrical resistance (TEER). Interestingly, delta-9-tetrahydrocannabinol (9-THC) treatment restored TEER to levels observed with control miRNA mimic. Finally, ex-vivo 9-THC treatment of colon tissue from chronically SIV-infected RMs significantly increased PPAR gene expression. Our findings suggest that dysregulated miR-130a and miR-212 expression in CE during chronic HIV/SIV infection can facilitate epithelial barrier disruption by downregulating OCLN and PPAR protein expression. Most importantly, our results highlight the beneficial effects of cannabinoids on epithelial barrier function in not just HIV/SIV but potentially other chronic intestinal inflammatory diseases.
2018-02-01 | GSE104767 | GEO
Project description:This study describes a circulating miRNA signature of acute retroviral infection, which may include candidate diagnostic or prognostic miRNAs for lentivirus-associated neurologic conditions. Plasma samples were taken from six macaques prior to infection and at ten days post-infection. Three macaques each went on to develop no or severe encephalitis. miRNA profiles were generated for each animal before and 10 days after SIV infection.
2011-09-14 | E-GEOD-26057 | biostudies-arrayexpress
Project description:The study describes miRNA expression in Oropharyngeal tissue of chronically SIV-infected rhesus macaques. To identify the underlying molecular mechanisms we simultaneously profiled miRNA and mRNA expression in oropharyngeal tissues of chronically simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs). Relative to controls, we identified 48 (38-upregulated and 10 downregulated) differentially expressed (DE) miRNAs relative to uninfected controls (n=5). Interestingly, in terms of magnitude, miR-19a, miR-301, miR-142-3p, miR-32 and miR-142-5p were among a select list of miRNAs that showed the highest upregulation in OPM. An important finding is the significant upregulation in OPM of miR-21, a microRNA known to regulate periodontitis, T-cell activation and oral carcinoma. Interestingly, RNA-seq for gene expression profiling also confirmed miR-21 upregulation in OPM of VEH-untreated/SIV rhesus macaques. Using TargetScan 7.2, we identified TSC22D3 (TSC22-domain family member 3), an anti-inflammatory protein induced by glucocorticoids and IL10 that was significantly downregulated in OPM of VEH-untreated/SIV macaques to be a predicted target of miR-29b. TSC22D3 localized to minor salivary gland acini and secretory ducts and showed reduced expression in OPM of VEH-untreated chronically SIV macaques. Using luciferase reporter and overexpression assays, we confirmed TSC22D3 to be a direct target of miR-29b. Interestingly, expression of miR-150 was significantly downregulated, a miRNA we previously demonstrated to be downregulated during T cell activation in the intestine. These findings strongly support a role for differential miRNA expression associated with HIV/SIV induced oropharyngeal mucosal dysfunction.
2020-07-01 | GSE150662 | GEO
Project description:The study describes miRNA expression in colon tissue following delta 9 tetrahydrocannabinol (Δ9-THC) administration to chronically SIV-infected rhesus macaques. To identify the underlying molecular mechanisms underlying its anti-inflammatory effects, we simultaneously profiled miRNA and mRNA expression in colon of chronically simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs) administered either vehicle (VEH/SIV; n=9) or Δ9- tetrahydrocannabinol (THC; THC/SIV; n=8). Relative to controls, differentially expressed miRNAs were ~2 fold higher in VEH/SIV than THC/SIV RMs. Proinflammatory miR-130a, miR-222 and miR-29b, Lipopolysaccharide-responsive miR-146b-5p and SIV-induced miR-190b were significantly upregulated in VEH/SIV RMs. Compared to VEH/SIV RMs, 10 miRNAs were significantly upregulated in THC-SIV RMs, among which miR-204 was confirmed to directly target MMP8, an extracellular matrix-degrading collagenase that was significantly downregulated in THC/SIV RMs. Moreover, THC/SIV RMs failed to upregulate proinflammatory miR-21, miR-141 and miR-222 and alpha/beta defensins, suggesting attenuated intestinal inflammation. Further, THC/SIV RMs showed higher expression of tight junction proteins (occludin, claudin-3), anti-inflammatory MUC13, keratin-8 (stress protection), PROM1 (epithelial proliferation) and anti-HIV CCL5. Trichrome mason staining detected significant collagen deposition (fibrosis) in the paracortex and B cell follicular zones of axillary lymph nodes from all VEH/SIV but none of the THC/SIV RMs, thus demonstrating the ability of THC to prevent lymph node fibrosis, a serious irreversible consequence of HIV induced chronic inflammation. Furthermore, using flow cytometry, we showed that THC suppressed intestinal T cell proliferation/activation (Ki67/HLADR) and exhaustion (PD1) and increased the percentages of anti-inflammatory CD163+ macrophages. Finally, while THC did not affect CD4+ T cell levels, it significantly reduced CD8+ T cell percentages in blood at 150 and 180 days post SIV infection. These translational findings strongly support a role for differential miRNA/gene induction and T cell activation in THC-mediated suppression of intestinal inflammation in HIV/SIV and potentially other chronic inflammatory diseases of the intestine.
2019-01-01 | GSE121440 | GEO
Project description:miRNA expression changes in small intestinal lamina propria leukocyte samples during the course of SIV infection of rhesus macaques
| PRJNA309527 | ENA
Project description:Simian Immunodeficiency Virus (SIV) infected rhesus macaques
| PRJNA765696 | ENA