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Genome-wide DNA methylation analysis reveals dynamic changes in metabolic and immune-regulatory pathways during uncontrolled SIV infection

ABSTRACT: Genome-wide DNA methylation analysis reveals dynamic changes in metabolic and immune-regulatory pathways during uncontrolled SIV infection

PROVIDER: PRJNA601421 | ENA |

REPOSITORIES: ENA

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Genome-wide DNA methylation analysis reveals dynamic changes in metabolic and immune-regulatory pathways during uncontrolled SIV infection

Project description:The molecular mechanisms underlying HIV-induced inflammation remain incompletely defined although they associate with morbidity and progression to AIDS. Here we used non-human primate models of pathogenic and nonpathogenic simian immunodeficiency virus (SIV) infection in respectively macaques and African green monkeys. We longitudinally analyzed DNA methylation changes in CD4+ T cells from lymph node and blood using species-compatible probes on human 450K methylation BeadArrays. Selected identified sites were validated using bisulfite-pyrosequencing of an independent cohort of uninfected, viremic and SIV controller macaques. Tissue- and species-specific DNA methylation changes were observed after SIV infection. The most affected genes in pathogenic SIV infection were related to metabolic pathways and Th1 signaling. SIV-infected macaques displayed increased insulin sensitivity early in the chronic phase of infection, which correlated with T cell activation. Moreover, DNA methylation changes in the Th1 pathway were associated with altered gene expression. Out of the 11 selected genes for validation, six genes showed differential methylation in viremic and uninfected macaques. In contrast, no significant differences were found between uninfected and SIV-controller macaques. In summary, pathogenic SIV infection associates with DNA methylation changes in genes related to metabolism and immune-regulation.

2020-12-15 | GSE143708 | GEO

Methamphetamine increases the proportion of SIV-infected microglia/macrophages, alters metabolic pathways, and elevates cell death pathways: a single-cell analysis

Project description:Both drugs abuse and HIV infection continue to affect many indiviiduals. Both have untoward effects on the brain, and the two conditions often co-exist. In the brain, macrophages and microglia are infectable by HIV, and these cells are also targets for the effects of drugs of abuse such as the psychostimulant methamphetamine. In order to determine the interaction of HIV and methamphetamine we isolated microglia and macrophages from the brains of SIV-infected rhesus monkeys treated with methamphetamine and from SIV-infected monkeys who did not receive methamphetamine. Cells were subjected to single cell RNA sequencing and results analyzed by statistical and bioinformatic analysis. In the animals treated with methamphetamine, a significantly increased proportion of cells were infected by SIV. In addition, genes encoding functions in cell death pathways were increased, and the brain-derived neurotropic factor pathway was inhibited. The gene expression patterns in infected cells did not cluster separately from uninfected cells, but clusters comprised of cells from methamphetamine-treated animals differed in neuroinflammatory and metabolic pathways from those comprised of cells from untreated animals. Methamphetamine increases CNS infection by SIV and has adverse effects on both infected and uninfected microglia and brain macrophages, highlighting the dual and interacting harms of HIV infection and drug abuse on the brain.

2020-12-01 | GSE160384 | GEO

Metabolic Pathways

Project description:This workspace holds a bond graph model of metabolic pathways.

| b91 | Physiome Model Repository

Methamphetamine increases the proportion of SIV-infected microglia/macrophages, alters metabolic pathways, and elevates cell death pathways: a single-cell analysis

Project description:Methamphetamine increases the proportion of SIV-infected microglia/macrophages, alters metabolic pathways, and elevates cell death pathways: a single-cell analysis

| PRJNA673143 | ENA

Distinct SIV-specific lymphoid tissue CD8 T cells exhibit simultaneous effector and stem-like profiles and associate with limited SIV persistence

Project description:HIV cure efforts are increasingly focused on harnessing CD8 T cell functions; however, a deeper understanding of CD8 T cells promoting HIV control is necessary to properly inform therapeutic approaches. Here, we identified a novel TOX-expressing CD8 T cell population associated with control of SIV infection in lymphoid tissue of rhesus macaques defined as an antigen-responsive TCF1+ CD39+ subset expressing high levels of TOX and inhibitory receptors but lower levels of canonical cytolytic molecules such as granzyme B, granzyme A, and perforin. Transcriptional analysis of SIV-specific CD8 T cells, as well as proteomic analysis of purified CD8 T cell subsets, revealed these TCF1+ CD39+ cells as an intermediate effector population retaining stem-like features while maintaining a lineage relationship with terminal effector cells. TCF1+ CD39+ CD8 T cells expressed higher levels of CXCR5 than terminally differentiated cells, were found at higher frequency in follicular micro-environments, and were preferentially located in the proximity of SIV-RNA+ cells both in lymph node T cell zone and B cell follicles. Importantly, their frequency was strongly associated with reduced plasma viremia and lower reservoir size. Finally, we confirmed the presence of a highly similar TOX-enriched TCF1+ CD39+ cell population in lymph node biopsies from ART-naïve and ART-treated people living with HIV. Collectively, these data identify a unique population of lymphoid CD8 T cells possessing both stem-like and effector properties that contribute to limiting HIV/SIV persistence.

2024-06-11 | PXD050498 | Pride

Severe Uncontrolled Asthma Lung Epithelial Brushing Gene Expression

Project description:Transcriptional profiling of lung epithelial brushing mRNA from severe uncontrolled asthmatics

2017-06-06 | GSE65584 | GEO

Dynamic changes of muscle insulin sensitivity after metabolic surgery

Project description:Dynamic changes of muscle insulin sensitivity after metabolic surgery

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Canagliflozin impairs T-cell effector function via metabolic suppression in autoimmunity [Metabolic Pathways]

Project description:Canagliflozin impairs T-cell effector function via metabolic suppression in autoimmunity [Metabolic Pathways]

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Microarray Expression Analysis of SIV infection of Sooty Mangabeys

Project description:Natural SIV infection of sooty mangabeys (SMs) does not progress to disease despite chronic virus replication. In contrast to pathogenic SIV infection of rhesus macaques (RMs), chronic SIV infection of SMs is characterized by low immune activation. To elucidate the mechanisms underlying this phenotype, we longitudinally assessed host gene expression in SIV-infected SMs and RMs. We found that acute SIV infection of SMs is consistently associated with a robust innate immune response, including widespread up-regulation of interferon-stimulated genes (ISGs). Our findings indicate that active immune regulatory mechanisms, rather than intrinsically attenuated innate immune responses, underlie the low immuneactivation of chronically SIV-infected SMs. We infected 5 SMs with SIVsmm and assessed their gene expression in RNA derived from whole blood at 3,7,10,14,30 and 180 days post-infection using Rhesus Affymetrix GeneChips. As a comparison, we also analyzed gene expression in 4 RMs infected with SIVsmm, and 8 RMs infected with SIVmac239, a classical pathogenic SIV.

2010-03-08 | E-GEOD-16147 | biostudies-arrayexpress

Microarray Expression Analysis of SIV infection of Sooty Mangabeys

2010-03-08 | GSE16147 | GEO