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: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: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:The differential expression of metabolic genes between effector and exhausted CD8+ Tcells has been characterized in the people living with HIV (PLWH) using 768 genes from the NanoString Human Metabolic Pathways Panel.
2024-07-01 | GSE270720 | GEO
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
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 | GSE165708 | GEO
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 | GSE165705 | GEO
Project description:Background: Atherosclerosis (AS)-associated cardiovascular disease is an important cause of mortality in an aging population of people living with HIV (PLWH). This elevated risk of atherosclerosis has been attributed to viral infection, prolonged usage of anti-retroviral therapy, and subsequent chronic inflammation. Methods: To investigate dysregulated immune signaling in PLWH with and without AS, we sequenced 9368 peripheral blood mononuclear cells (PBMCs) from 8 PLWH, 4 of whom also had atherosclerosis (AS+). To develop executable models of signaling pathways that drive cellular states in HIV-associated atherosclerosis, we developed the single-cell Boolean Omics Network Invariant Time Analysis (scBONITA) algorithm. ScBONITA (a) uses single-cell RNA sequencing data to infer Boolean rules for topologically characterized networks, (b) prioritizes genes based on their impact on signaling, (c) performs pathway analysis, and (d) maps sequenced cells to characteristic signaling states. We used scBONITA to identify dysregulated pathways in different cell-types from AS+ PLWH and AS- PLWH. To compare our findings with pathways associated with HIV infection, we used scBONITA to analyze a publicly available dataset of PBMCs from subjects before and after HIV infection. Additionally, the executable Boolean models characterized by scBONITA were used to analyze observed cellular states corresponding to the steady states of signaling pathways Results: We identified an increased subpopulation of CD8+ T cells and a decreased subpopulation of monocytes in AS+ PLWH. Dynamic modeling of signaling pathways and pathway analysis with scBONITA provided a new perspective on the mechanisms of HIV-associated atherosclerosis. Lipid metabolism and cell migration pathways are induced by AS rather than by HIV infection. These pathways included AGE-RAGE and PI3K-AKT signaling in CD8+ T cells, and glucagon and cAMP signaling pathways in monocytes. Further analysis of other cell subpopulations suggests that the highly interconnected PI3K-AKT signaling pathway drives cell migratory state in response to dyslipidemia. scBONITA attractor analysis mapped cells to pathway-specific signaling states that correspond to distinct cellular states. Conclusions: Dynamic network modeling and pathway analysis with scBONITA indicates that dysregulated lipid signaling regulates cell migration into the vascular endothelium in AS+ PLWH. Attractor analysis with scBONITA facilitated pathway-based characterization of cellular states that are not apparent in gene expression analyses.
2022-09-06 | GSE198339 | GEO
Project description:The aim of this discovery case-control study was to identify patterns of differential expression of microRNAs in people living with HIV (PLWH) and assess their diagnostic value for non-alcoholic fatty liver disease (NALFD). Cases were defined as patients with severe NAFLD and controls as patients without NAFLD, characterized using the controlled attenuation parameter (CAP). Cases and controls were matched 1:1 for age, sex, body mass index, CD4+ lymphocyte count, active HCV infection, and ART regimen. Serum 2,083 simultaneous microRNA transcripts were analyzed using HTG technology and compared between cases and controls. Forty-five patients, 23 cases, and 22 controls were included in the study. In the analysis of the expression pattern of the 2,083 microRNAs, no differential expression patterns were found between both groups of patients included in the study. Analysis of the microRNA transcriptome profile of nonobese PLWH with severe NAFLD did not appear to differ from that of patients without NAFLD. Thus, microRNA might not serve as a proper biomarker for predicting severe NALFD in this population.
2023-05-03 | E-MTAB-12974 | biostudies-arrayexpress