HIV-1 Amplifies IL-8 Response Of Human Stellate Cells To Gram-Positive Microbial Products Via H4K5 Histone Acetylation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE324653 | GEO | 2026/03/13
REPOSITORIES: GEO
Similar Datasets
Project description:Chronic liver disease is becoming a leading cause of illness and mortality in people living with human immunodeficiency virus (HIV) (PLWH) undergoing suppressive anti-retroviral therapy. Its main etiology has been reported to be coinfection with hepatitis B (HBV) and C (HCV) viruses. Accumulating evidence indicate chronic liver inflammation and fibrosis can potentially lead to the development of hepatocellular carcinoma (HCC). Therefore, monitoring of the disease progression in PLWH is required. The present study aimed to explore the plasma protein profiles of patients with HIV infection and those coinfected with HBV and HCV using shotgun proteomics.
2024-06-29 | PXD053504 | JPOST Repository
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: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:An effective broadly reactive antibody response is crucial to prevent viral infections. A small number of people living with HIV (PLWH) develop broadly neutralizing antibodies (bNAbs) targeting multiple HIV strains. We performed combined cell-free DNA (cfDNA) and cell-free RNA (cfRNA) sequencing in 42 plasma samples from a longitudinal cohort of 14 PLWH, of whom 7 developed bNAbs and 7 matched controls. cfRNA profiling revealed early immune activation signatures and distinct microbial associations linked to bNAb development.
2026-03-13 | GSE313190 | GEO
Project description:Antiretroviral therapy (ART) has the potency of suppressing systemic viral replication and spread. Still, persistent human immunodeficiency virus type-1 (HIV) survive for decades during treatment in latently infected cells, making up the latent viral reservoir. This reservoir is believed to reside in subtypes of memory T cells and cell from monocytic lineages, but some functional and naïve T cells have also shown to carry latent HIV. Eradication of latently infected cells, in terms of a sterilizing cure, have proven to be a hurdle since there is a heterogeneity in mechanisms governing latency and integration site into the genome. Over the course of suppressive therapy, persisting HIV, sustained by low levels of viral replication, homeostatic proliferation, and cell to cell transmission, is a driver of chronic immune activation in the body. For the immune system to elicit an appropriate inflammatory response it is dependent on secretion of inflammatory molecules, such as chemokines and cytokines. Most chemokines are pro-inflammatory factors that facilitate leukocyte recruitment to site of inflammation where they can exert their regulatory role in response to pathological and physiological stressors e.g., infection, inflammation, and tissue damage. Alterations in chemokine receptor expression and chemokine levels modulates the activity of the immune response and in HIV infection contribute to chronic inflammation and mortality. Therefore, people living with HIV on suppressive therapy (PLWH) are at higher risk of age associated co-morbidities due to elevated immune activation and chronic inflammation induced by ART toxicities, microbiome dysbiosis leading to microbial translocation and dysregulated immune cell activation and function. As a result, the causative HIV pathogenesis and immune dysfunction further chronic immune activation. This result in a vicious cycle as immune activation is driver of HIV disease progression and inflammaeging leading to earlier onset of age-related diseases. An alternative approach in cure strategies is a functional cure for HIV aiming at suppressing viral replication without ART. A model for functional cure studies are elite controllers (EC). EC constitute a small fraction of HIV+ individuals (<0.5%) exhibiting the unique characteristic of natural control of viral replication in absence of ART. However, there is a population-based heterogeneity of how these individuals naturally supress viral replication. This heterogeneity is caused by viral genetic factors, variability of integration site in the human genome, together with host response against the pathogen and immunological factors. In terms of immune cell activation, studies have shown how EC maintain lower levels of inflammatory markers compared to PLWH. Contradictory, some studies have shown elevated inflammatory markers in EC which could be attributed to the heterogeneity of the EC group or as others have shown it is a consequence of loss of spontaneous control of HIV. Therefore, as no consensus exist further studies comparing variability of immune function between EC and ART can aid in understanding the mechanisms of natural control of HIV. In our recent study (Sperk et al 2021, iScience) we hypothesised that modulated CCR6/CCL20 chemokine axis and CCR2-CCL7-CCL2 signalling can play a protective role in the EC phenotype. Downregulation of CCR2 and CCR6 receptors in lymphocytes and higher plasma abundance of CCL4, CCL7 and CCL20 in EC compared to the HIV-negative controls can provide natural resistance to HIV-infection. In the present study, we further extended our analysis to evaluate the expression profile dynamics of key chemokine receptors, CCR2, CCR3, CCR5 and CCR6, in successfully treated PLWH. We compared well treated PLWH with HIV-1 elite controllers and its association with HIV-1 persistence. Furthermore, cell populations of interest were isolated for liquid chromatography mass spectrometry (LC-MS/MS) based untargeted proteomics analysis to evaluate specific characteristics regulating these cell populations and their role in HIV persistence. Our study provides important understanding of the chemokine receptor dynamics and its role in HIV persistence that differentiate elite controllers from long term treated PLWH.
2022-04-22 | PXD027749 | Pride
Project description:Liver fibrosis is characterized by the activation of perivascular hepatic stellate cells (HSCs), the release of fibrogenic nano-sized extracellular vesicles (EVs) and increased HSC glycolysis. Nevertheless, how glycolysis in HSCs coordinates fibrosis amplification through tissue zone-specific pathways remains elusive. Here, we demonstrate that HSC-specific genetic inhibition of glycolysis reduced liver fibrosis. Moreover, spatial transcriptomics revealed a fibrosis-mediated upregulation of EV-related pathways in the liver pericentral zone, which was abrogated by the glycolysis genetic inhibition. Mechanistically, glycolysis in HSCs upregulated the expression of EV-related genes such as RAB31 by enhancing histone-3-lysine-9 acetylation on the promoter region, which increased EV release. Functionally, these glycolysis-dependent EVs increased fibrotic gene expression in recipient HSC. Furthermore, EVs derived from glycolysis-deficient mice abrogated liver fibrosis amplification in contrast to glycolysis-competent mouse EVs. In summary, glycolysis in HSCs amplifies liver fibrosis by promoting fibrogenic EV release in the hepatic pericentral zone, which represents a potential therapeutic target.
2024-05-16 | PXD050337 | Pride
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:Chronic liver injury can result in fibrosis that may progress over years to end-stage liver disease. The most effective antifibrotic therapy is treatment of the underlying disease, however when this is not possible, interventions to reverse fibrosis are needed. We conducted an open-label pilot trial to study the safety and tolerability of simtuzumab, a monoclonal antibody directed against lysyl oxidase-like 2 (LOXL2) enzyme, in patients with advanced liver disease from hepatitis C virus (HCV), human immunodeficiency virus (HIV), or HCV-HIV co-infection. 18 patients with advanced liver fibrosis received simtuzumab 700mg IV every 2 weeks for 22 weeks. There were no discontinuations due to adverse events. No significant change was seen in hepatic venous pressure gradient or liver biopsy fibrosis score after treatment. Exploratory transcriptional and protein profiling using paired pre- and post-treatment liver biopsies, serum, and whole blood identified upregulation of TGFβ3 and IL-10 pathways with treatment. In summary, simtuzumab was well tolerated in HCV- and HIV-infected patients with advanced liver disease. Modulation of TGFβ3 and IL-10 pathways as a result of simtuzumab treatment merits investigation in future trials.
2017-09-08 | GSE73634 | GEO
Project description:The lack of available biomarkers to diagnose and predict different stages of liver disease with a non-invasive strategy is currently one of the main challenges that clinicians are facing. Recent evidence indicates that the plasma levels of specific microRNAs (miRNAs) may be significantly altered in patients with liver injury, including human immunodeficiency virus type 1 (HIV-1) infected patients. Large-scale deep sequencing analysis of small RNA expression was performed on plasma samples from 46 HIV-1/hepatitis C virus (HCV) co-infected patients that did not exhibit liver fibrosis at the time of sampling. A total of 1065 different miRNAs were identified. After a mean of 10.3 years, 26 of the former patients developed liver fibrosis (stage F2-4) and 20 remained without signs of liver fibrosis (stage F0-1). We identified a signature of seven miRNAs, 100-5p, 192-5p, 99a-5p, 122-5p, 125b-2-3p, 1246 and 194-5p, that highly correlated with patients progressing to liver fibrosis. These seven miRNAs detected liver fibrosis progression with an area under curve (AUC) of 0.910-0.806. The two miRNAs, 100-5p and 192-5p, displaying the best AUC values, yielded both a sensitivity of 88% and a specificity of 85% for liver fibrosis progression. Our results demonstrate the predictive potential of circulating levels of miRNAs to foresee liver fibrosis progression even before liver fibrosis or significant clinical differences such as liver transaminases or platelets are detectable. Thus, our study might help in predicting the progression of liver injury in HIV-1-infected patients.
2021-11-08 | GSE161845 | GEO
Project description:Ductular reaction (DR) is the hallmark of cholestatic diseases manifested in the proliferation of bile ductules lined by biliary epithelial cells (BECs). It is commonly associated with increased risk of fibrosis and liver failure. The Receptor for Advanced Glycation End Products (RAGE) was identified as a critical mediator of DR during chronic injury. Yet, the direct link between RAGE-mediated DR and fibrosis as well as the mode of interaction between BECs and hepatic stellate cells (HSCs) to drive fibrosis remain elusive. Here, we delineate the specific function of RAGE on BECs during DR and its potential association with fibrosis in the context of cholestasis. Employing a biliary lineage tracing cholestatic liver injury mouse model, combined with whole transcriptome sequencing, mass spectrometry and in vitro analyses, we investigated the role for BEC-specific Rage activity in fostering a pro-fibrotic milieu. RAGE is predominantly expressed in BECs and contributes to DR. Employing mass spectrometry analyses of soluble factors of in vitro cultured wildtype and RAGE deficient BECs Notch ligand Jagged1 was found to be secreted from activated BECs in a Rage-dependent manner and signals HSCs in trans, eventually enhancing fibrosis during cholestasis.
2025-07-16 | PXD065854 | Pride