Dataset Information

Differences in HIV burden in the inflamed and non-inflamed colon from a person living with HIV and ulcerative colitis.

ABSTRACT: The greatest obstacle to an HIV cure is the persistence of latently infected cellular reservoirs in people living with HIV (PLWH) taking antiretroviral therapy (ART). However, no consensus exists on the direct link between local tissue inflammation and the HIV burden. Herein, we have compared the levels of local inflammation, epithelial integrity and HIV DNA between inflamed and non-inflamed colon tissue in a PLWH who underwent a colectomy due to ulcerative colitis. We have observed a 27-fold higher frequency of cells harboring HIV DNA in inflamed compared to non-inflamed colon tissue. Analysis of the expression of occludin-1 and claudin-3 confirmed our macroscopic characterization of inflamed and non-inflamed colon. Our results confirm that increased gut permeability and inflammation are associated with a higher frequency of infected cells and suggest that restoring gut barrier integrity may be used as a strategy to reduce inflammation and HIV persistence in the gut.

SUBMITTER: Peng X

PROVIDER: S-EPMC7906891 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Differences in HIV burden in the inflamed and non-inflamed colon from a person living with HIV and ulcerative colitis.

Peng Xiaorong X Isnard Stéphane S Lin John J Fombuena Brandon B Bessissow Talat T Chomont Nicolas N Routy Jean-Pierre JP

Journal of virus eradication 20210215 1

The greatest obstacle to an HIV cure is the persistence of latently infected cellular reservoirs in people living with HIV (PLWH) taking antiretroviral therapy (ART). However, no consensus exists on the direct link between local tissue inflammation and the HIV burden. Herein, we have compared the levels of local inflammation, epithelial integrity and HIV DNA between inflamed and non-inflamed colon tissue in a PLWH who underwent a colectomy due to ulcerative colitis. We have observed a 27-fold hi ...[more]

PMID: 33664976

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Project description:BackgroundUlcerative colitis (UC) is associated with differential colonic expression of genes involved in immune response (e.g. IL8) and barrier integrity (e.g. cadherins). MicroRNAs (miRNAs) are regulators of gene expression and are involved in various immune-related diseases. In this study, we investigated (1) if miRNA expression in UC mucosa is altered and (2) if any of these changes correlate with mucosal mRNA expression. Integration of mRNA and miRNA expression profiling may allow the identification of functional links between dysregulated miRNAs and their target mRNA.MethodologyColonic mucosal biopsies were obtained from 17 UC (10 active and 7 inactive) patients and 10 normal controls. Total RNA was used to analyze miRNA and mRNA expression via Affymetrix miRNA 2.0 and Affymetrix Human Gene 1.0ST arrays, respectively. Both miRNA and gene expression profiles were integrated by correlation analysis to identify dysregulated miRNAs with their corresponding predicted target mRNA. Microarray data were validated with qRT-PCR. Regulation of IL8 and CDH11 expression by hsa-miR-200c-3p was determined by luciferase reporter assays.ResultsWhen comparing active UC patients vs. controls, 51 miRNAs and 1543 gene probe sets gave significantly different signals. In contrast, in inactive UC vs. controls, no significant miRNA expression differences were found while 155 gene probe sets had significantly different signals. We then identified potential target genes of the significantly dysregulated miRNAs and genes in active UC vs. controls and found a highly significant inverse correlation between hsa-miR-200c-3p and IL8, an inflammatory marker, and between hsa-miR-200c-3p and CDH11, a gene related to intestinal epithelial barrier function. We could demonstrate that hsa-miR-200c-3p directly regulates IL8 and CDH11 expression.ConclusionDifferential expression of immune- and barrier-related genes in inflamed UC mucosa may be influenced by altered expression of miRNAs. Integrated analysis of miRNA and mRNA expression profiles revealed hsa-miR-200c-3p for use of miRNA mimics as therapeutics.

Dataset Information

Differences in HIV burden in the inflamed and non-inflamed colon from a person living with HIV and ulcerative colitis.

Publications

Differences in HIV burden in the inflamed and non-inflamed colon from a person living with HIV and ulcerative colitis.

Similar Datasets

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