An aberrant resurrection of endogenous retrovirus prompts acute myocarditis and heart failure
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1148419 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The abberant resurgence of which have been recently found to link to some critical pathologies. To evaluate the occurrence and role of ERV resurrgenece in heart and heart failure (HF), we conducted heart total RNA-seq analysis from mice ischemia-reperfusion (I/R) heart failure models and found that ERVs were activated which is similar in various cross-species models of heart failure. To explore the mechanism of ERVs resurgence we profiled trimethylation at lysine 9 of histone H3 (H3K9me3) ChIP- and MeRIP-seq of cardiomyocytes specific TRIM28 knockout mice heart. The deprivation of TRIM28 in the mouse myocardium attenuated the epigenetic surveillance of H3K9me3 and N6-methyladenosine (m6A), and revived the ERVs, which consequently activated the intracellular antiviral innate immune pathways of TLR7-9 and NF-kappaB and lead to the myocarditis and acute heart failure.
2025-08-20 | GSE274895 | GEO
Project description:The human genome is replete with sequences derived from foreign elements including endogenous retrovirus-like proteins of unknown function. The human genome is replete with sequences derived from foreign elements including endogenous retrovirus-like proteins of unknown function. Here we show that UBQLN2, a ubiquitin-proteasome shuttle factor implicated in neurodegenerative diseases, is regulated by the linked actions of two retrovirus-like proteins, RTL8 and PEG10. RTL8 confers on UBQLN2 the ability to complex with and regulate PEG10. PEG10, a core component of stress granules, drives the recruitment of UBQLN2 to stress granules under various stress conditions, but can only do so when RTL8 is present. Changes in PEG10 levels further remodel the kinetics of stress granule disassembly and overall composition by incorporating select extracellular vesicle proteins. Within stress granules, PEG10 forms virus-like particles, underscoring the structural heterogeneity of this class of biomolecular condensates. Together, these results reveal an unexpected link between pathways of cellular proteostasis and endogenous retrovirus-like proteins. we show that UBQLN2, a ubiquitin-proteasome shuttle factor implicated in neurodegenerative diseases, is regulated by the linked actions of two retrovirus-like proteins, RTL8 and PEG10. RTL8 confers on UBQLN2 the ability to complex with and regulate PEG10. PEG10, a core component of stress granules, drives the recruitment of UBQLN2 to stress granules under various stress conditions, but can only do so when RTL8 is present. Changes in PEG10 levels further remodel the kinetics of stress granule disassembly and overall composition by incorporating select extracellular vesicle proteins. Within stress granules, PEG10 forms virus-like particles, underscoring the structural heterogeneity of this class of biomolecular condensates. Together, these results reveal an unexpected link between pathways of cellular proteostasis and endogenous retrovirus-like proteins.
2025-06-04 | PXD061852 | Pride
Project description:RNA-Seq data from the resurrection plant Xerophyta schlechteri during desiccation in three tissues: non-senescent, senescent and pre-senescent during dehydration and rehydration.
2022-12-30 | GSE168229 | GEO
Project description:Sequencing data of biopsies from Myocarditis and DCM patients
2018-09-28 | GSE120567 | GEO
Project description:Immune checkpoint inhibitors (ICIs) are improving cancer treatments strikingly. The raising use leads to the augmented occurrence of immune related events. Myocarditis is a rare, but severe form of these adverse events. Nine patients with proven ICI induced myocarditis were subjected to myocardial biopsy. The tissue was used for RNA-seq analyses.
2020-11-01 | E-MTAB-8867 | biostudies-arrayexpress
Project description:Cryptic endogenous retrovirus subfamilies in the primate lineage
| PRJNA1029531 | ENA
Project description:Lymphocytic myocarditis is characterized by infiltration of lymphocytes and macrophages. Current treatment for lymphocytic myocarditis is limited to corticosteroids and a proportion of patients progress to require heart transplantation or durable mechanical circulatory support within a year. Increasing attention is directed toward targeting pro-inflammatory mediators in myocarditis. One promising candidate is IL-1. Here, we investigated a patient with underlying autoimmune disease and biopsy confirmed lymphocytic myocarditis who was initially treated with corticosteroids and experienced clinical deterioration requiring temporary mechanical circulatory support. Rilonacept was consequently administered as a salvage therapy. Pathologically, rilonacept reduced inflammation and fibrosis. We performed spatial transcriptomics (ST) on formalin-fixed paraffin-embedded endomyocardial biopsy samples to further investigate how the cardiac immune landscape is modulated by rilonacept.
2025-07-09 | GSE296452 | GEO
Project description:Dilated cardiomyopathy vs Myocarditis
| PRJNA493608 | ENA
Project description:Extracellular vesicles (EVs) can potently inhibit inflammation yet there is a lack of understanding about the impact of donor characteristics on the efficacy of EVs. The goal of this study was to determine whether the sex and age of donor platelet-derived EVs (PEV) affected their ability to inhibit viral myocarditis. PEV, isolated from men and women of all ages, was compared to PEV obtained from women under 50 years of age, which we termed premenopausal PEV (pmPEV). Because of the protective effect of estrogen against myocardial inflammation, we hypothesized that pmPEV would be more effective than PEV at inhibiting myocarditis. We injected PEV, pmPEV, or vehicle control in a mouse model of viral myocarditis and examined histology, gene expression, protein profiles, and performed proteome and microRNA (miR) sequencing of EVs. We found that both PEV and pmPEV significantly inhibited myocarditis; however, PEV was more effective, which was confirmed by a greater reduction of inflammatory cells and proinflammatory and profibrotic markers determined using gene expression and immunohistochemistry. Proteome and miR sequencing of EVs revealed that PEV miRs specifically targeted antiviral, Toll-like receptor (TLR)4, and inflammasome pathways known to contribute to myocarditis while pmPEV contained general immunoregulatory miRs. These differences in EV content corresponded to the differing anti-inflammatory effects of the two types of EVs on viral myocarditis.
2024-12-30 | PXD058698 | Pride
Project description:Immune checkpoint inhibitors (ICIs), antibodies targeting PD-1/PD-L1 or CTLA4 have revolutionized cancer management but are associated with devastating immune-related adverse events (irAEs) including myocarditis. The main risk factor for ICI myocarditis is the use of combination PD-1 and CTLA4 inhibition. ICI-myocarditis is often fulminant and is pathophysiologically characterized by myocardial infiltration of T lymphocytes and macrophages. While much has been learned regarding the role of T-cells in ICI-myocarditis, little is understood regarding the identity, transcriptional diversity, and functions of infiltrating macrophages. We employed an established murine ICI myocarditis model (Ctla4+/-Pdcd1-/- mice) to explore the cardiac immune landscape using single-cell RNA-sequencing, immunostaining, and molecular imaging. We observed marked increases in CCR2+ monocyte-derived macrophages and CD8+ T-cells in this model. The macrophage compartment was heterogeneous and displayed marked enrichment in an inflammatory CCR2+ subpopulation expressing Cxcl9, Cxcl10, Gbp2b, and Fcgr4 that originated from CCR2+ monocytes. Importantly, a similar macrophage population expressing CXCL9, CXCL10, and CD16α (human homologue of mouse FcgR4) were found selectively in patients with ICI myocarditis compared to other forms of heart failure and myocarditis. In silico prediction of cell-cell communication suggested interactions between T-cells and Cxcl9+Cxcl10+ macrophages via IFN-γ and CXCR3 signaling pathways. Depleting CD8+T-cells and blockade of IFN-γ signaling blunted the emergence of Cxcl9+Cxcl10+ macrophages in the heart and attenuated myocarditis suggesting that this interaction was necessary for disease pathogenesis. Collectively, these data demonstrate that ICI-myocarditis is associated with the emergence of a specific population of inflammatory macrophages and suggest the possibility that IFN-γ blockade may serve as an effective treatment for this devastating condition.
2023-07-01 | GSE227437 | GEO