Ontology highlight
ABSTRACT:
PROVIDER: PRJNA798435 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17675723_1.fastq.gz | Fastqsanger.gz | |||
| SRR17675723_2.fastq.gz | Fastqsanger.gz | |||
| SRR17675724_1.fastq.gz | Fastqsanger.gz | |||
| SRR17675724_2.fastq.gz | Fastqsanger.gz | |||
| SRR17675725_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 48 |
Similar Datasets
Project description:Rare cases of non-hepatotropic virus (NHV) infection in humans can cause severe hepatitis and even acute liver failure. Clinically relevant animal models of NHV-induced hepatitis are limited, contributing to the incomplete understanding of pathological mechanisms. Murine norovirus (MNV) elicits hepatosplenomegaly in mice lacking the antiviral immune effector Signal Transducer and Activator of Transcription-1 (STAT1), providing a model to investigate mechanisms of NHV-induced hepatic pathology. STAT1-sufficient and -deficient (Stat1Het, Stat1KO) littermates infected intravenously (i.v.) with MNV strain CR6 were assessed for hepatic inflammation and viral burden. Cell types and molecular pathways associated with hepatic pathology in CR6-infected Stat1KO mice were identified by flow cytometry and RNAseq of liver tissue. The relative importance of hematopoietic vs non-hematopoietic expression of STAT1 in restricting CR6 replication and maintaining tissue homeostasis was assessed in bone marrow chimeras. MNV CR6 Stat1KO mice developed severe hepatitis with patchy hepatocellular necrosis and localized enrichment of CR6-infected myeloid cells, particularly macrophages. Gene set enrichment analysis (GSEA) of hepatic biopsies isolated from CR6-infected Stat1KO mice suggested dysregulated myeloid cell activation and indicated similarities between murine and human hepatic pathologies. STAT1 expression in hematopoietic cells was protective against hepatic viral dissemination, but hematopoietic STAT1-deficiency permitted persistent hepatic MNV infection, facilitating dysregulated myeloid cell activation and hepatic fibrosis. These results demonstrate that the role of STAT1 extends beyond restricting MNV dissemination and suggest that STAT1-dependent regulation of myeloid cell activation prevents acute hepatic necroinflammation and secondary fibrosis. This model of MNV-induced hepatitis may prove valuable in elucidating mechanisms of rare clinical complications.
2026-05-01 | GSE326527 | GEO
Project description:Interferonopathies drive autoimmunity but can also impair host responses to pathogens including viral infection. To better understand viral susceptibility of patients with STAT1 gain-of-function (GOF) mutations, we generated conditional-knockin mouse models to elucidate disease mechanisms and relevance of different immune subsets. Virally infected Stat1-GOF mice exhibited impaired early IFN-γ production from innate lymphocytes, and lethality due to excess prolonged multi-cytokine production. The presence of the Stat1-GOF allele resulted in premature usage of interferon-stimulated gene factor 3 (ISGF3) over the normal Stat4/AP-1 dependent transcriptomic program in activated innate lymphocytes. Administration of anti-IFN-γantibodies in wild-type (WT) mice after infection phenocopied Stat1-GOF mice presenting exaggerated inflammation despite viral control. Conversely, early administration of exogenous IFN-γ to infected Stat1-GOF mice prevented lethality and exaggerated cytokine response.Although Stat1-GOF mutations facilitate IFN-γ-mediated autoimmunity, early IFN-γ response to viral infection via a normal Stat4 program was impaired, leading to overcompensated inflammatory responses in Stat1-GOF mice.
2025-06-13 | GSE284323 | GEO
Project description:Interferonopathies drive autoimmunity but can also impair host responses to pathogens including viral infection. To better understand viral susceptibility of patients with STAT1 gain-of-function (GOF) mutations, we generated conditional-knockin mouse models to elucidate disease mechanisms and relevance of different immune subsets. Virally infected Stat1-GOF mice exhibited impaired early IFN-γ production from innate lymphocytes, and lethality due to excess prolonged multi-cytokine production. The presence of the Stat1-GOF allele resulted in premature usage of interferon-stimulated gene factor 3 (ISGF3) over the normal Stat4/AP-1 dependent transcriptomic program in activated innate lymphocytes. Administration of anti-IFN-γantibodies in wild-type (WT) mice after infection phenocopied Stat1-GOF mice presenting exaggerated inflammation despite viral control. Conversely, early administration of exogenous IFN-γ to infected Stat1-GOF mice prevented lethality and exaggerated cytokine response.Although Stat1-GOF mutations facilitate IFN-γ-mediated autoimmunity, early IFN-γ response to viral infection via a normal Stat4 program was impaired, leading to overcompensated inflammatory responses in Stat1-GOF mice.
2025-06-13 | GSE284322 | GEO
Project description:Interferonopathies drive autoimmunity but can also impair host responses to pathogens including viral infection. To better understand viral susceptibility of patients with STAT1 gain-of-function (GOF) mutations, we generated conditional-knockin mouse models to elucidate disease mechanisms and relevance of different immune subsets. Virally infected Stat1-GOF mice exhibited impaired early IFN-γ production from innate lymphocytes, and lethality due to excess prolonged multi-cytokine production. The presence of the Stat1-GOF allele resulted in premature usage of interferon-stimulated gene factor 3 (ISGF3) over the normal Stat4/AP-1 dependent transcriptomic program in activated innate lymphocytes. Administration of anti-IFN-γantibodies in wild-type (WT) mice after infection phenocopied Stat1-GOF mice presenting exaggerated inflammation despite viral control. Conversely, early administration of exogenous IFN-γ to infected Stat1-GOF mice prevented lethality and exaggerated cytokine response.Although Stat1-GOF mutations facilitate IFN-γ-mediated autoimmunity, early IFN-γ response to viral infection via a normal Stat4 program was impaired, leading to overcompensated inflammatory responses in Stat1-GOF mice.
2025-06-13 | GSE284176 | GEO
Project description:It is well known that IFNα/β activates the JAK/STAT signaling pathway and suppresses viral replication through induction of interferon stimulated genes (ISGs). Here we reported that knockout of HDAC3 from macrophages resulted in decreased expression of STAT1 and STAT2, leading to a defective anti-viral immunity in cells and mice. Further studies showed that HDAC3 interacted with a conserved transcription factor Forkhead Box K1 (FOXK1), co-localized with FOXK1 at the promoter of STAT1 and STAT2, and was required for protecting FOXK1 from lysosomal system mediated degradation. Constantly, FOXK1 deficient macrophages also showed low STAT1 and STAT2 expression with defective response to virus. Thus, our studies uncovered the biological importance of HDAC3 on regulating antiviral immunity of macrophages through interaction with FOXK1 to regulate the expression of STAT1 and STAT2.
2022-05-12 | GSE190578 | GEO
Project description:It is well known that IFNα/β activates the JAK/STAT signaling pathway and suppresses viral replication through induction of interferon stimulated genes (ISGs). Here we reported that knockout of HDAC3 from macrophages resulted in decreased expression of STAT1 and STAT2, leading to a defective anti-viral immunity in cells and mice. Further studies showed that HDAC3 interacted with a conserved transcription factor Forkhead Box K1 (FOXK1), co-localized with FOXK1 at the promoter of STAT1 and STAT2, and was required for protecting FOXK1 from lysosomal system mediated degradation. Constantly, FOXK1 deficient macrophages also showed low STAT1 and STAT2 expression with defective response to virus. Thus, our studies uncovered the biological importance of HDAC3 on regulating antiviral immunity of macrophages through interaction with FOXK1 to regulate the expression of STAT1 and STAT2.
2022-05-12 | GSE190577 | GEO
Project description:Mouse norovirus (MNV) causes acute or chronic infection in immunocompetent hosts, but the CD8 T cell determinants of viral persistence versus clearance are unknown. We used microarrays to interrogate the transcriptional program on MNV-specific CD8 T cells from the spleen and intestine at days 8, 15, 30 post infection with and acute or chronic strain of MNV.
2017-07-24 | GSE101429 | GEO
Project description:Purpose: Characterisation of MNV induced host genetic reprogramming and translational control exerted over the host response by comparison of available cytoplasmic transcripts and their association with polysomes. Results: RNaseq data showed an inadequate response to MNV infection downstream of MDA5 activation coupled with a cellular response to a metabolic stress. In particular, all 296 significantly regulated transcripts showed a strong correlation between a transcript availability in the cytoplasm and its recrutment to the polysomal fraction as addressed using the R package 'Anota2seq'. Genome annotation analyses using Cytoscape highlighted the host response to the viral infection but showed a cluster of genes involved in response to stress and the related intrinsic apoptotic pathways suggesting a prevalence of a metabolic stress response over the innate immune response to the viral replication. Conclusions: Our study provides the first understanding analysis of the host response to MNV at the level of available cytoplasmic mRNA and their recruitment to the actively translating fractions. It described an absence of translational control over the host innate immune response but highlight and inadequate NF-kB response correlating with an ectopic anti-inflammatory response to amino acid starvation.
2021-07-14 | GSE168402 | GEO
Project description:Since its discovery over three decades ago, signal transducer and activator of transcription 1 (STAT1) has been extensively studied as a central mediator for interferons (IFNs) signaling and antiviral defense. Here, using genetic and biochemical assays, we unveil Thr748 as a conserved IFN-independent phosphorylation switch in Stat1, which restricts IFN signaling and promotes innate inflammatory responses following the recognition of the bacterial-derived toxin lipopolysaccharide (LPS). Genetically-engineered mice expressing phospho-deficient threonine748–to-alanine (T748A) mutant Stat1 are resistant to LPS–induced lethality. Of note, T748A mice exhibited undisturbed IFN signaling, as well as total expression of Stat1. Further, the T748A point-mutation of Stat1 recapitulates the safeguard effect of the genetic ablation of Stat1 following LPS-induced lethality, indicating that the Thr748 phosphorylation contributes inflammatory functionalities of Stat1. Mechanistically, LPS-induced Toll-like receptor 4 endocytosis activates a cell-intrinsic IκB kinase (IKK)–mediated Thr748 phosphorylation of Stat1, which promotes macrophages inflammatory response while restricting the IFN and anti-inflammatory responses. Depletion of macrophages restores the sensitivity of the T748A mice to LPS-induced lethality. Together, our study indicates a phosphorylation-dependent functional dichotomy of Stat1 in innate immune responses: IFN phospho-tyrosine dependent, and inflammatory phospho-threonine dependent. Better understanding of the Thr748 phosphorylation of Stat1 may uncover novel pharmacologically targetable molecules and offer better treatment modalities for sepsis, a disease that claims millions of lives annually.
2024-03-18 | GSE261824 | GEO
Project description:Stringent regulation of the interferon signaling pathway is essential for maintaining the immune response to pathogens and tumors. The transcription factor STAT1 is a crucial mediator of this response. Here we show that hCAF1/CNOT7 regulates class I and II interferon pathways at different crucial steps. In resting cells hCAF1 can control STAT1 trafficking by interacting with the latent form of STAT1 in the cytoplasm. IFN treatment induces STAT1 release, suggesting that hCAF1 may shield cytoplasmic STAT1 from undesirable stimulation. Consistent, hCAF1 silencing enhances STAT1 basal promoter occupancy associated with increased expression of a subset of STAT1-regulated genes. Consequently, hCAF1 knockdown cells exhibit an increased protection against viral infection and reduced viral replication. Furthermore, hCAF1 participates in the extinction of the IFN signal, through its deadenylase activity, by speeding up the degradation of some STAT1-regulated mRNAs. Since abnormal and unbalanced JAK/STAT activation is associated with immune disorders and cancer, hCAF1 could play a major role in innate immunity and oncogenesis, contributing to tumor escape. mRNAs from cells expressing the siRNA siRNA duplexes targeting hCAF1, corresponding to the coding region 941-961 (kd) (hCAF1 NCBI Reference Sequence: NM_013354.5) and one non-targeting control siRNA (mock).
2013-12-31 | E-GEOD-43334 | biostudies-arrayexpress