Blood RNA sequencing in HIV-negative healthy volunteers and people living with HIV on effective, long-term anti-retroviral therapy
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PROVIDER: PRJEB37238 | ENA |
REPOSITORIES: ENA
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Project description:Immune activation in people living with HIV on anti-retroviral therapy is associated with increased risk of morbidity and mortality, but the underlying mechanisms are poorly understood. To identify whether perturbation of immunological pathways persist at systems level, we compared genome-wide whole blood transcriptomes from 26 people living with HIV on long-term anti-retroviral therapy with 12 HIV-negative healthy controls. All participants were Caucasian male adults recruited from London, UK. People living with HIV were on anti-retroviral therapy for a median of 8.5 years (interquartile range 3-16 years). They had undetectable plasma HIV viral load (<40 copies/ml) and median circulating CD4 counts of 703 cells/µl (interquartile range 491-841 cells/µl).
2021-02-26 | E-MTAB-8891 | biostudies-arrayexpress
Project description:In this study we performed data-independet mass-spectrometry analysis of blood plasma collected from a cohort consisting of people living with HIV-1, people living with HIV-2, and HIV seronegative individuals. The data was used to infer signs of damage to a wide array of tissues and cell types.
2024-02-16 | PXD045155 | Pride
Project description:Myeloid dendritic cells (mDC) were isolated from antiretroviral therapy (ARV)-treated and untreated people living with HIV (PLWH), and from HIV uninfected Individuals. The results indicate that mDC are altered in genes expression from PLWH. Some RNA transcriptional changes are not completely restored by ARV. This provides more data on myeloid cells, an understudied cell type, and alterations in PLWH.
2020-01-10 | GSE139559 | GEO
Project description:Whole genome transcriptional profiling by microarray of blood taken from HIV-negative healthy volunteers (n=15), and HIV patients before (n=24) and after three months of anti-retroviral therapy (n=17). This submission includes two human whole genome Agilent Array Designs: A-AGIL-28 and A-GEOD-20844. Each of the individual raw array files are included as well as a single processed file representing the data matrix of all the merged and normalised data for the probes that are shared by the two array designs.
2021-02-26 | E-MTAB-8897 | biostudies-arrayexpress
Project description:Antiretroviral therapy (ART) is not curative due to the existence of cellular reservoirs of latent HIV-1 that persist during therapy 1. Current research efforts to cure HIV-1 infection include “shock and kill” strategies to disrupt latency using small molecules or latency-reversing agents (LRAs) to induce expression of HIV-1 enabling cytotoxic immune cells to eliminate infected cells 2. However, the modest success of current LRAs urges the field to identify novel drugs with increased clinical efficacy 3,4. Aminobisphosphonates that include pamidronate, zoledronate, or alendronate, are the first-line treatment of bone-related diseases including osteoporosis and bone malignancies 5. Here, we show the use of aminobisphosphonates as a novel class of LRA: we found in ex vivo assays using primary cells from ART-suppressed people living with HIV-1 that aminobisphosphonates induce HIV-1 from latency to levels that are comparable to the T cell activator phytohemagglutinin. RNA sequencing and mechanistic data suggested that reactivation may occur through activation of the activator protein 1 signaling pathway. Stored samples from a prior clinical trial aimed at analyzing the effect of alendronate on bone mineral density, provided further of alendronate-mediated latency reversal and activation of immune effector cells.Decay of the reservoir measured by IPDA was however not detected. Our results demonstrate the novel use of aminobisphosphonates to reverse HIV-1 latency while inducing immune effector functions. This preliminary evidence merits further investigation in a controlled clinical setting possibly in combination with therapeutic vaccination.
2023-09-13 | GSE224546 | GEO
Project description:Myeloid Dendritic Cells from People Living with HIV have Altered Gene Expression Not Restored by Anti-Retroviral Therapy
| PRJNA580248 | ENA
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:<p>Rare individuals are highly resistant to infection with human immunodeficiency virus (HIV). Studies of candidate genes resulted in the discovery of a 32bp deletion in the CC-chemokine receptor 5 gene (CCR5Δ32), which rendered this critical co-receptor for primary HIV infection to be non-functional. Pharmacologic and vaccine-induced blockade of CCR5 is being pursued to treat and prevent HIV infection and other conditions.</p> <p>The allele frequency of CCR5Δ32 among persons of European ancestry is approximately 10%. CCR5Δ32/Δ32 homozygotes are almost totally resistant to HIV infection. People with severe hemophilia A require frequent replacement with clotting Factor VIII (FVIII) to control hemorrhage. Prior to the discovery of HIV in 1984 and licensure of recombinant FVIII in the late 1980s, people with severe hemophilia A were treated with plasma-derived FVIII and thus were intensively exposed to HIV. Only 5% of such patients were not infected with HIV. Of these, approximately 1/3 were CCR5Δ32/Δ32 homozygotes. The remaining 2/3 of these people who were highly resistant to HIV remain unexplained. This project seeks to discover genome variations among people who are highly resistant to HIV infection. Such variation is likely to serve as a target for reducing the morbidity and incidence of HIV. </p>
| phs000445.v1.p1 | EGA
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: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