Myeloid Dendritic Cells from People Living with HIV have Altered Gene Expression Not Restored by Anti-Retroviral Therapy
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE139559 | GEO | 2020/01/10
REPOSITORIES: GEO
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Project description:Background: Although acquired immunodeficiency syndrome-related mortality has decreased since the introduction of antiretroviral therapy, the incidence of lung cancer in patients living with HIV (PLWH) remains high. Understanding the effects of tobacco smoke on airway gene expression in PLWH may provide insight into the elevated lung cancer risk associated with HIV. Methods: Airway epithelial brushings were collected from 12 PLWH who smoke and 19 PLWH who have never smoked and profiled using RNA-seq. Linear models were used to identify genes differentially expressed between people who smoke and have never smoked and between people who previously smoked and have never smoked. Gene set enrichment analysis was used to validate smoking-related gene signatures across datasets. Data was integrated with gene expression data from a cohort of patients without HIV to identify genes differentially modulated by both smoking and HIV status. Results: We found that previous smoking-related gene signatures are similarly associated with smoking in PLWH, including the persistent differential expression of a subset of "irreversibly altered" genes in people who previously smoked compared to people who have never smoked. We also identified and validated two gene signatures specifically modulated in people who smoke without HIV. Conclusions: Many of the effects of smoking on bronchial gene expression are shared between PLWH and non-HIV individuals. Of the subset of genes that differ between PLWH and non-HIV individuals, it appears that the effect of smoking on gene expression is more attenuated in PLWH. This includes genes related to oxidative stress and epithelial integrity, and suggests potential mechanisms that may contribute to smoking-related outcomes that are more prevalent in PLWH, such as lung cancer.
2026-02-05 | GSE318533 | GEO
Project description:<p>Objective: The gut microbiome plays a pivotal role in human immunodeficiency virus (HIV) infection. However, the associated alterations in the gut microbiome-host interaction remain unclear. This study aims to investigate the gut microbiota and fecal metabolites in people living with HIV (PLWH).</p><p>Method: We collected stool samples from 70 PLWH and 34 healthy controls (HCs) and performed 16S rRNA gene sequencing. Metabolite analysis was conducted using liquid chromatography-mass spectrometry.</p><p>Results: Firmicutes, Proteobacteria, Actinobacteriota, and Bacteroidota were the most abundant phyla in both groups. At the genus level, Escherichia Shigella was significantly upregulated in the PLWH group, whereas Bacteroides were upregulated in the HC group. Functional prediction of the microbiota indicated significant reductions in alanine, aspartate, and glutamate metabolism, as well as histidine metabolism. Furthermore, comparison of fecal metabolites between the HC and PLWH groups identified 38 differentially abundant metabolites across four enriched human metabolic pathways. Spearman correlation analysis revealed close relationships between four differentially abundant microbiota members and five differentially abundant fecal metabolites, which may influence specific human metabolic pathways.</p><p>Conclusion: Our findings provide a foundation for further experimental investigations into the contribution of the gut microbiota and its associated metabolites to HIV/AIDS, offering a novel perspective for future studies on HIV/AIDS.</p>
2024-09-16 | MTBLS9264 | MetaboLights
Project description:HIV-related comorbidities appear to be related to chronic inflammation, a condition characterizing people living with HIV (PLWH). Prior work indicates that cannabidiol (CBD) might reduce inflammation; however, the genetics underpinning this effect are not well investigated. Our main objective is to detect gene expression alterations in human peripheral blood mononuclear cells (PBMCs) from PLWH after at least one month of CBD treatment. We collected PBMCs from three HIV-positive subjects at baseline and after CBD treatment (at least 27 days) via single-cell RNA sequencing. We obtained a coherent signature, characterized by an anti-inflammatory activity, of differentially expressed genes in myeloid cells. Our study shows how CBD is associated with alterations of gene expression in myeloid cells after CBD treatment.
2023-03-31 | GSE228652 | GEO
Project description:Background: Age-related comorbidities remain a burden in People living with HIV (PLWH). DNA methylation may be a link between HIV, aging, and the increased risk of lung comorbidities. Here, we investigate whether bronchoalveolar lavage (BAL) cells of PLWH demonstrate epigenome wide disruptions and advanced epigenetic aging. Methods: BAL cell DNA methylation profiles from 25 PLWH and 16 uninfected controls were tested for differential methylation of transposable elements Alu and LINE-1, a marker of aging. We used a weighted gene correlation network analysis to identify co-methylation networks associated with HIV and age. We tested the effect of HIV on DNA methylation using a robust linear model. An enrichment analysis was conducted to identify differentially methylated pathways (false discovery rate <0.10). Results: The BAL cells of PLWH were marked by global hypomethylation in both Alu and LINE-1 elements. Six co-methylated CpG networks were identified that were significantly associated with age; of these, the red module was significantly differentially methylated in PLWH and enriched pathways associated with HIV, Ras signaling, T cell receptors, and bacterial invasion of epithelial cells. We identified 6,428 differentially methylated sites associated with HIV. Conclusions: We have shown here for the first time that alterations in the DNA methylation of BAL cells (mainly macrophages) in the lung HIV show in a pattern of advanced aging. In conjunction with our findings in blood cells and airway cells, this study strongly support that HIV may contribute to increase the risk of lung comorbidities through the epigenetic regulation of aging.
2024-07-03 | GSE262656 | GEO
Project description:People living with HIV (PLWH) experience chronic intestinal barrier dysfunction (gut leakage), which persists despite viral suppression by antiretroviral therapy (ART) and contributes to chronic inflammation and its comorbidities. The mechanisms underlying this phenomenon remain unclear and are likely multifactorial. We hypothesize that living with HIV compromises the intestinal barrier’s resilience to injurious agents, increasing susceptibility to leakage upon exposure to common exogenous or endogenous disruptors, such as alcohol or pro-inflammatory cytokines, respectively. Using 3D intestinal organoids (colonoids and enteroids) derived from PLWH on ART and HIV-negative controls, we assessed the impact of alcohol and inflammatory cytokines on barrier integrity. Organoids from PLWH exhibited reduced resilience to disruption compared to controls, correlating with alterations in pathways critical to epithelial integrity, including epithelial-mesenchymal transition, DNA repair, and oxidative stress-related pathways. These findings reveal a novel mechanism underlying intestinal dysfunction in PLWH and highlight potential molecular targets to mitigate these complications.
2025-12-17 | GSE284755 | GEO
Project description:People living with HIV (PLWH) experience chronic intestinal barrier dysfunction (gut leakage), which persists despite viral suppression by antiretroviral therapy (ART) and contributes to chronic inflammation and its comorbidities. The mechanisms underlying this phenomenon remain unclear and are likely multifactorial. We hypothesize that living with HIV compromises the intestinal barrier’s resilience to injurious agents, increasing susceptibility to leakage upon exposure to common exogenous or endogenous disruptors, such as alcohol or pro-inflammatory cytokines, respectively. Using 3D intestinal organoids (colonoids and enteroids) derived from PLWH on ART and HIV-negative controls, we assessed the impact of alcohol and inflammatory cytokines on barrier integrity. Organoids from PLWH exhibited reduced resilience to disruption compared to controls, correlating with alterations in pathways critical to epithelial integrity, including epithelial-mesenchymal transition, DNA repair, and oxidative stress-related pathways. These findings reveal a novel mechanism underlying intestinal dysfunction in PLWH and highlight potential molecular targets to mitigate these complications.
2025-12-17 | GSE284761 | GEO
Project description:Despite successful combination antiretroviral therapy (cART), persistent low-grade immune activation together with inflammation and toxic antiretroviral drugs can lead to long-lasting metabolic flexibility and adaptation in people living with HIV (PLWH). Our study investigated alterations in the plasma metabolic profiles by comparing PLWH on long-term cART(>5years) and matched HIV-negative controls (HC) in two cohorts from low- and middle-income countries (LMIC), Cameroon and India, respectively to understand the system-level dysregulation in HIV-infection. Using untargeted and targeted LC-MS/MS-based metabolic profiling and applying advanced system biology methods, an altered amino acid metabolism, more specifically to glutaminolysis in PLWH than HC were reported. A significantly lower level of neurosteroids were observed in both cohorts and could potentiate neurological impairments in PLWH. Further, modulation of cellular glutaminolysis promoted increased cell death and latency reversal in pre-monocytic HIV-1 latent cell model U1, which may be essential for the clearance of the inducible reservoir in HIV-integrated cells.
2021-11-24 | PXD028531 | Pride
Project description:Despite the introduction of combined antiretroviral therapy (cART), people living with HIV (PLWH) still have an increased risk of EBV-associated B cell malignancies. In the HIV setting, B cell physiology is altered by co-existence with HIV-infected cells and the chronic action of secreted viral proteins, e.g. HIV-1 Tat that, once released, efficiently penetrates non-infected cells. Here we modeled a chronic action of HIV-1 Tat on B cells by ectopically expressing Tat or its mutant version TatC22G deprived of transactivation activity in two EBV-immortalized lymphoblastoid B cell lines. RNA-sequencing analysis revealed that Tat regulated the expression of hundreds of genes, including downregulation of a subset of genes related to MHC class II. Tat-induced transcriptional downregulation of HLA-DRB1, HLA-DRB5 genes was accompanied by a decrease in HLA-DR surface expression; this effect could be reproduced by co-cultivating B cells with Tat-expressing T cells. Notably, HLA-DRB1 expression in B cells was also decreased in PLWH. Chronic Tat presence decreased the NF-ᴋB pathway activity; this downregulated NF-ᴋB-dependent transcriptional targets, including MHC class II genes. Tat-induced HLA-DR downregulation in B cells also impaired EBV-specific CD4+ T cell response, which could contribute to the escape from immune surveillance and eventually promote B cell lymphomagenesis.
2022-09-04 | GSE212499 | GEO
Project description:Background: Despite effective antiretroviral therapy and sustained viral suppression, people living with HIV (PLWH) continue to exhibit persistent immune activation and low-grade inflammation. Although the CD4/CD8 ratio is routinely monitored as a marker of immune health, the mechanisms underlying residual immune dysregulation remain incompletely understood. Methods: Peripheral blood mononuclear cells from PLWH and HC were collected before and one month after two doses of mRNA vaccination and analyzed by single-cell RNA sequencing with paired TCR profiling. Differential gene expression (DGE) and protein–protein interaction (PPI) network analyses were performed, and node degree distributions were compared among groups. TCR and bulk BCR repertoires were analyzed, and neutralizing antibody responses were assessed. PLWH were stratified by CD4/CD8 ratio. Results: Stratification by CD4/CD8 ratio revealed distinct immune states in PLWH. Differential genes from the normal CD4/CD8 ratios showed focused transcriptional activation with coordinated chemokine-associated communication, whereas those with low CD4/CD8 ratios exhibited broad transcriptional dysregulation and structural reorganization of gene-expression networks. This network signature was characterized by altered PPI topology and significantly increased monocyte-specific node degree, independent of overall transcriptional complexity. Repertoire analyses demonstrated clonal skewing and reduced clonotype diversity in the low CD4/CD8 ratio group, consistent with impaired immune coordination. Conclusion: Vaccine-induced immune responses in PLWH are shaped by network-level organization associated with CD4/CD8 ratio–defined immune states. Low CD4/CD8 ratio group showed increased monocyte-specific PPI connectivity and clonal imbalance, suggesting altered vaccine-induced response dynamics not captured by conventional clinical markers.
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Project description:Persons living with HIV (PLWH) are at increased risk of tuberculosis (TB). HIV-associated TB is mainly the result of recent infection with Mycobacterium tuberculosis (Mtb) followed by rapid progression to disease. Alveolar macrophages (AM) are the first cells of the innate immune system that engage Mtb, but how HIV and antiretroviral therapy (ART) impact on the anti-mycobacterial response of AM is not known. In this study AM were challenged in vitro with Mtb, and their epigenetic and transcriptomic responses were determined for PLWH receiving ART, control subjects who were HIV-free (HC) and subjects who received pre-exposure prophylaxis (PrEP) with ART to prevent HIV infection. Compared to HC subjects’ response to Mtb, we showed that AM isolated from PLWH and PrEP subjects displayed substantially weaker transcriptomic response and no significant changes in their chromatin state. These findings revealed a previously unknown adverse effect of ART.
2021-09-03 | GSE165703 | GEO