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ABSTRACT:
PROVIDER: PRJNA630982 | ENA |
REPOSITORIES: ENA
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Project description:Compartmentalized HIV Rebound in the Central Nervous System after Interruption of Antiretroviral Therapy
| PRJEB14227 | ENA
Project description:A growing body of data suggests that the human brain serves as a sanctuary for HIV persistence despite life-long antiretroviral therapy. Microglia, the innate immune cells of the brain parenchyma, may serve as a reservoir for rebound of HIV infection. The extent of the latent brain reservoir and molecular phenotype of HIV infected microglia cells, however, are unknown. To address this major knowledge gap, we leveraged the ‘Last Gift’ rapid autopsy cohort to perform a multi-omics approach (single cell RNA-seq, single cell ATAC-seq, and H3K27ac ChIP-seq) of the myeloid compartment creating a gene expression and chromatin accessibility atlas of human microglia isolated from three male individuals with HIV on suppressive antiretroviral therapy.
2024-02-01 | GSE221686 | GEO
Project description:A growing body of data suggests that the human brain serves as a sanctuary for HIV persistence despite life-long antiretroviral therapy. Microglia, the innate immune cells of the brain parenchyma, may serve as a reservoir for rebound of HIV infection. The extent of the latent brain reservoir and molecular phenotype of HIV infected microglia cells, however, are unknown. To address this major knowledge gap, we leveraged the ‘Last Gift’ rapid autopsy cohort to perform a multi-omics approach (single cell RNA-seq, single cell ATAC-seq, and H3K27ac ChIP-seq) of the myeloid compartment creating a gene expression and chromatin accessibility atlas of human microglia isolated from three male individuals with HIV on suppressive antiretroviral therapy.
2024-02-01 | GSE221685 | GEO
Project description:A growing body of data suggests that the human brain serves as a sanctuary for HIV persistence despite life-long antiretroviral therapy. Microglia, the innate immune cells of the brain parenchyma, may serve as a reservoir for rebound of HIV infection. The extent of the latent brain reservoir and molecular phenotype of HIV infected microglia cells, however, are unknown. To address this major knowledge gap, we leveraged the ‘Last Gift’ rapid autopsy cohort to perform a multi-omics approach (single cell RNA-seq, single cell ATAC-seq, and H3K27ac ChIP-seq) of the myeloid compartment creating a gene expression and chromatin accessibility atlas of human microglia isolated from three male individuals with HIV on suppressive antiretroviral therapy.
2024-02-01 | GSE221687 | GEO
Project description:We compared transcriptional profiles of CD4+ and CD8+ T lymphocytes from HIV infected individuals before and 1 year after interruption of antiretroviral therapy (ART).
2018-01-01 | GSE98902 | GEO
Project description:The development of biomarkers that can predict viral rebound following discontinuation of antiretroviral therapy (ART) in HIV-1-infected humans would be an important advance in HIV-1 cure research. In a prior study, we initiated ART in 20 rhesus macaques on days 0, 1, 2, and 3 following SIVmac251 infection prior to plasma viremia1. Following 6 months of suppressive ART, we discontinued ART and observed viral rebound in 9 of 20 animals. Here we show that transcriptomic and proteomic signatures of inflammation and immune activation in peripheral blood during ART suppression predicted viral rebound following ART discontinuation. Higher levels of proinflammatory and cellular immune activation pathways, including TNF, IL-1, IL-6, monocyte, and T cell activation signaling pathways, correlated with viral rebound following ART discontinuation. Immune modulatory IL-10 and TGF-b signaling also correlated with viral rebound. We then validated these candidate biomarkers of viral rebound in a second cohort of SIV-infected, ART-suppressed macaques. Taken together, these data suggest that persistent upregulation of inflammatory and immune activation pathways despite suppressive ART may represent a peripheral blood biomarker signature of the rebound-competent viral reservoir. The development of interventions that target the viral reservoir and modulate this signature may open new avenues in HIV-1 cure research.
2023-08-30 | GSE203603 | GEO
Project description:Objective: This study aimed to evaluate the effect of dendritic cell (DC) vaccination against HIV-1 on host gene expression profiles. Design: Longitudinal PBMC samples were collected from participants of the DC-TRN trial for immunotherapy against HIV. Microarray-assisted gene expression profiling was performed to evaluate the effects of vaccination and subsequent interruption of antiretroviral therapy on host genome expression. Data from the DC-TRN trial were compared with results from other vaccination trials. Methods: We used Affymetrix GeneChips for microarray gene expression analysis. Data were analyzed by principal component analysis and differential gene expression was assessed using linear modeling. Gene ontology enrichment and gene set analysis were used to characterize differentially expressed genes. Transcriptome analysis included comparison with PBMCs obtained from DC-vaccinated melanoma patients and of healthy individuals who received seasonal influenza vaccination. Results: DC-TRN immunotherapy in HIV-infected individuals resulted in a major shift in the transcriptome. Longitudinal analysis demonstrated that changes in the transcriptome sustained also during interruption of antiretroviral therapy. After DC-vaccination, the transcriptome was enriched for cellular immunity associated genes that were also induced in healthy adults who received live attenuated influenza virus vaccination. These beneficial responses were accompanied by detrimental signals of general immune activation. Conclusions: The DC-TRN induced changes in the transcriptome were profound, lasting, and consisted of both protective signals and signatures of inflammation and immune exhaustion, with a net result of decreased viral load, without clinical benefit. Thus transcriptome analysis provides useful information, dissecting both positive and negative effects, for the evaluation of safety and efficacy of immunotherapeutic strategies.
2015-04-30 | E-MTAB-3296 | biostudies-arrayexpress
Project description:The BCN02 (NCT02616874) was a pilot study to evaluate the kick and kill therapy on 15 early-treated individuals that were rolled-over from the BCN01 Study. The participants in the study received two MVA.HIVconsv vaccination before and after the 3-cycle infusion of Romidepsin, an inhibitor of histone deacetylases that act as a latency reversing agent. Additionally, the inclusion of a monitored antiretroviral pause (MAP) allowed tthe identification of 8 individuals with an Early Rebound (pVL > 2,000 HIV RNA copies/mL, < 4 weeks of MAP initiation) and 4, with a Late Rebound (pVL > 2,000 HIV RNA copies/mL, > 4 weeks of MAP initiation). In the present study we studied gene expression at 3 different timepoints: w0 (Bsl), w1 (Vacc), w6 (Vacc+RMD) and applied pairwise comparisons.
2022-03-28 | GSE184653 | GEO
Project description:Memory CD4 T cells facilitate HIV establishment following transmission and contribute to HIV persistence during suppressive antiretroviral therapy (ART). Numerous studies have highlighted the importance of memory CD4 T cells expressing the surface integrin heterodimer, α4β7 in HIV infection. Here, we focused on delineating the molecular characteristics of α4β7+ CD4 T cells and determining how transcriptional profiles of circulating α4β7hi CD4 T cells corresponded to that within the lower GI tract.
2021-01-21 | GSE165213 | GEO
Project description:In people with HIV (PWH), the post antiretroviral therapy (ART) window is critical for immune restoration and HIV reservoir stabilization. We employ deep immune profiling, T cell receptor (TCR) sequencing and examine proliferation to assess how ART impacts T cell homeostasis. Hierarchies and frequencies of dominant CD4 TCR clonotypes (0.1-11% of all CD4+ T cells) remain stable post-ART, suggesting that clonal homeostasis can be independent of homeostatic processes regulating CD4+T cell absolute number, phenotypes and function. The slow restoration of host-immunity post-ART also has implications for the design of ART interruption studies.
2023-10-09 | GSE244867 | GEO