Kinetic analysis of mouse brain proteome alterations following Chikungunya virus infection before and after appearance of clinical symptoms.
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Instrument
ORGANISM(S): Mus_musculus_viruses, Chikungunya_virus, Mouse_female
DISEASE(S): Not Available
SUBMITTER: 
Fraisier C, et al.
PROVIDER: GPM32320016202 | GPMDB |
REPOSITORIES: GPMDB
Similar Datasets
Project description:A kinetic analysis of host proteome modifications in the brain of CHIKV-infected mice sampled before and after the onset of clinical symptoms was performed. The combination of 2D-DIGE and iTRAQ proteomic approaches, followed by mass spectrometry protein identification, revealed 177 significantly differentially expressed proteins. This kinetic analysis was characterized by a dramatic down-regulation of proteins prior the appearance of the clinical symptoms followed by an increase expression of a large part of these proteins in the acute phase of symptoms. Bioinformatic analysis of the protein dataset allowed to identify major biological processes altered during the time course of CHIKV infection such as integrin signaling and cytoskeleton dynamics, endosome machinery and receptor recycling related to virus transport and synapse function, regulation of gene expression, and ubiquitin-proteasome pathway. This work gives new information on putative mechanisms that could be associated with severe neurological CHIKV infection-mediated disease. It also describes possible markers or targets that can be used to develop diagnostic and/or antiviral tools.
2015-07-07 | PXD000736 | Pride
Project description:The gut microbiota can influence brain function and behaviour through several mechanisms. The first critical step that initiates microbial-host interaction which leads to the establishment of normal behavior is unknown. In this study, we identified that activation of the innate immune system by microbes is a critical step in the initiation of the gut-brain communication. We showed that bacterial mono-colonization was sufficient to initiate the normalization of behavior which critically depends on Toll-like receptors. To investigate the mechanisms by which immune system activation affects behavior, we assessed the brain region specific (hippocampus and amygdala) gene expression from germ-free Swiss Webster mice before and after mono-colonization with E.coli HA107 bacterial strain. Gene expression analysis showed that colonization affected multiple pathways related to innate immunity and neuronal function, including canonical pathway of glucocorticoid receptor that play key role in regulating emotion and cognition. Several genes directly involved in neuronal plasticity were altered by colonization, including phenotypic switch in NMDA receptors subunits, which in conventional animals is observed after birth and possibly linked to initial exposure to microbiome. These results raise the possibility that impaired postnatal microbiota-host cross talk could affect normal brain maturation process and lead to altered neurodevelopment and psychiatric disorders later in life.
2025-12-01 | GSE138320 | GEO
Project description:The major inducible 70 kDa heat shock protein (hsp70) is host protective in a mouse model of measles virus (MeV) brain infection. Transgenic constitutive expression of hsp70 in neurons, the primary target of MeV infection, abrogates neurovirulence in neonatal H-2d congenic C57BL/6 mice. A significant level of protection is retained after depletion of T lymphocytes, implicating innate immune mechanisms. Focus of the present work was to elucidate the basis for hsp70-dependent innate immunity using this model. Transcriptome analysis of brains from transgenic (TG) and non-transgenic (NT) mice 5 days after infection identified type 1 interferon (IFN) signaling and macrophage activation/antigen presentation as the main differences linked to survival. The pivotal role for type 1 IFN in hsp70-mediated protection was demonstrated in mice with a genetically disrupted type 1 IFN receptor (IFNAR-/-), where IFNAR-/- eliminated the difference in survival between TG and NT mice. Brain macrophages, not neurons, are the predominant source of type 1 IFN in the virus-infected brain, and in vitro studies provided a mechanistic basis by which MeV-infected neurons can induce IFN-β in uninfected microglia in an hsp70-dependent manner. MeV infection induced extracellular release of hsp70 from mouse neuronal cells that constitutively express hsp70, and extracellular hsp70 induced IFN-β transcription in mouse microglial cells through Toll-like receptors 2 and 4. Collectively, results support a novel axis of type 1 IFN-dependent antiviral immunity in the virus-infected brain that is driven by hsp70. Hsp70 expression in mice enhances gene expression related to antiviral immune response against MeV neurovirulence. We performed microarrays on whole brain tissues in mice to obtain an unbiased picture of how hsp70 alters host innate responses to viral infection. Hsp70-overexpressing transgenic (TG) and non-transgenic (NT) mice were infected with MeV intracranially, and total brain mRNA harvested at 5 and 10 days post infection (d.p.i.) was analyzed, sampling the hemisphere opposite the side of viral inoculation. Analysis includes 6 groups: infected TG at 5 d.p.i. (n=4), infected TG at 10 d.p.i. (n=5), infected NT at 5 d.p.i. (n=4), infected NT at 10 d.p.i. (n=5), uninfected TG at 5 d.p.i. (n=4), and uninfected NT at 5 d.p.i. (n=4).
2012-11-14 | E-GEOD-42264 | biostudies-arrayexpress
Project description:Mardinoglu2015 - Tissue-specific genome-scale
metabolic network - Brain cortex
This model is described in the article:
The gut microbiota modulates
host amino acid and glutathione metabolism in mice.
Mardinoglu A, Shoaie S, Bergentall
M, Ghaffari P, Zhang C, Larsson E, Bäckhed F, Nielsen
J.
Mol. Syst. Biol. 2015; 11(10):
834
Abstract:
The gut microbiota has been proposed as an environmental
factor that promotes the progression of metabolic diseases.
Here, we investigated how the gut microbiota modulates the
global metabolic differences in duodenum, jejunum, ileum,
colon, liver, and two white adipose tissue depots obtained from
conventionally raised (CONV-R) and germ-free (GF) mice using
gene expression data and tissue-specific genome-scale metabolic
models (GEMs). We created a generic mouse metabolic reaction
(MMR) GEM, reconstructed 28 tissue-specific GEMs based on
proteomics data, and manually curated GEMs for small intestine,
colon, liver, and adipose tissues. We used these functional
models to determine the global metabolic differences between
CONV-R and GF mice. Based on gene expression data, we found
that the gut microbiota affects the host amino acid (AA)
metabolism, which leads to modifications in glutathione
metabolism. To validate our predictions, we measured the level
of AAs and N-acetylated AAs in the hepatic portal vein of
CONV-R and GF mice. Finally, we simulated the metabolic
differences between the small intestine of the CONV-R and GF
mice accounting for the content of the diet and relative gene
expression differences. Our analyses revealed that the gut
microbiota influences host amino acid and glutathione
metabolism in mice.
This model is hosted on
BioModels Database
and identified by:
MODEL1509220013.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2015-11-04 | MODEL1509220013 | BioModels
Project description:Mardinoglu2015 - Tissue-specific genome-scale
metabolic network - Brain medulla
This model is described in the article:
The gut microbiota modulates
host amino acid and glutathione metabolism in mice.
Mardinoglu A, Shoaie S, Bergentall
M, Ghaffari P, Zhang C, Larsson E, Bäckhed F, Nielsen
J.
Mol. Syst. Biol. 2015; 11(10):
834
Abstract:
The gut microbiota has been proposed as an environmental
factor that promotes the progression of metabolic diseases.
Here, we investigated how the gut microbiota modulates the
global metabolic differences in duodenum, jejunum, ileum,
colon, liver, and two white adipose tissue depots obtained from
conventionally raised (CONV-R) and germ-free (GF) mice using
gene expression data and tissue-specific genome-scale metabolic
models (GEMs). We created a generic mouse metabolic reaction
(MMR) GEM, reconstructed 28 tissue-specific GEMs based on
proteomics data, and manually curated GEMs for small intestine,
colon, liver, and adipose tissues. We used these functional
models to determine the global metabolic differences between
CONV-R and GF mice. Based on gene expression data, we found
that the gut microbiota affects the host amino acid (AA)
metabolism, which leads to modifications in glutathione
metabolism. To validate our predictions, we measured the level
of AAs and N-acetylated AAs in the hepatic portal vein of
CONV-R and GF mice. Finally, we simulated the metabolic
differences between the small intestine of the CONV-R and GF
mice accounting for the content of the diet and relative gene
expression differences. Our analyses revealed that the gut
microbiota influences host amino acid and glutathione
metabolism in mice.
This model is hosted on
BioModels Database
and identified by:
MODEL1509220000.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2015-11-03 | MODEL1509220000 | BioModels
Project description:This project investigates the molecular and cellular mechanisms that enable HIV persistence within the human brain across distinct infection states. Postmortem brain tissues from uninfected controls, viremic individuals, and antiretroviral therapy (ART) suppressed people with HIV were dissociated into single-nucleus suspensions and profiled by high-throughput RNA sequencing. The resulting dataset supports the identification of transcriptional reprogramming, immune modulation, and latent viral reservoir signatures associated with HIV-associated neurocognitive disorders (HAND). Integration of single-nucleus RNA-seq data across these clinical conditions provides a comprehensive atlas of HIV host interactions in the central nervous system.
2026-05-19 | GSE331008 | GEO
Project description:SARS-CoV-2 and, to a lesser extent, influenza A can lead to long-term complications in the respiratory and nervous systems. However, the mechanisms driving post-viral sequelae remain poorly understood. To address this gap, we longitudinally characterized C57BL/6 mice infected with sublethal doses of mouse-adapted SARS-CoV-2 (MA30) or influenza A (PR8). Lung and brain tissues were analyzed at 14-, 21-, and 28-days post-infection (DPI) using histological analysis and bulk-RNA sequencing. In the lungs, both infections caused prolonged inflammation and fibrosis. MA30-infected lungs showed persistent upregulation of inflammatory, coagulation, complement, as well as fibrotic, and extracellular matrix (ECM) remodeling pathways at 21 DPI, alongside downregulation of epithelial junction and metabolic program pathways. In contrast, PR8-infected lungs exhibited a strong acute interferon response and chronic upregulation of basal epithelial markers (e.g., Krt5, Krt14), consistent with epithelial regeneration. Notably, only PR8-infected mice displayed KRT5+ progenitor cell migration into damaged lung regions, indicating divergence in repair mechanisms. Neither MA30-infected, nor PR8-infected mice had detectable brain infection. However, MA30 mice, but not PR8-infected mice exhibited an elevated frequency of microhemorrhages at early timepoints and marked neuroinflammation at all timepoints. Transcriptomic profiling of MA30-infected brains showed enrichment for up-regulation of ECM remodeling, vascular dysfunction, IL6-signaling pathways along with a virus-specific disruption of the hypothalamic–pituitary axis with MA30 infection not seen in PR8-infected brains. These included genes linked to neuroinflammation, sensory processing disruption, and microvascular injury, mirroring clinical features of Long COVID. Together, these findings establish distinct tissue-specific trajectories of long-term pathology following SARS-CoV-2 and influenza infection and provide a foundation for dissecting the mechanisms of post-viral lung and brain disease.
2026-01-12 | GSE315893 | GEO
Project description:Molecular mechanisms for changing brain connectivity in mice and humans (brain samples)
| PRJNA1022783 | ENA
Project description:To investigate the relationship between the host factor APOBEC1 and the viral factor vUNG in the pathogenesis of herpes encephalitis, wild-type and Apobec1-deficient mice were infected with vUNG mutants and their repaired strains. Brain tissues were collected, and host mRNA expression was analyzed using RNA sequencing.
2025-04-02 | GSE276253 | GEO
Project description:Neurocysticercosis, caused by the establishment of Taenia solium larvae in the central nervous system, is a leading cause of acquired epilepsy and neurological morbidity in endemic regions. Viable cysticerci can persist in the brain for years with minimal inflammation, whereas parasite degeneration, either spontaneous or induced by antiparasitic treatment, triggers intense inflammatory and vascular responses. Despite the clinical relevance of this transition, the host transcriptional changes associated with viable infection and early post-treatment lesions remain poorly understood. We performed the first bulk RNA sequencing analysis of brain tissue from experimentally infected pigs, a physiologically relevant model of human neurocysticercosis. We compared transcriptional profiles from uninfected controls (n=3), infected untreated pigs with viable clear-capsule cysts (n=6), and infected pigs treated with albendazole plus praziquantel with disrupted blue-capsule lesions (n=3). Differential expression and pathway enrichment analyses were used to characterise host responses associated with infection and treatment. Neurocysticercosis infection was associated with altered expression of genes involved in immune activation, together with reduced vascular- and endothelial-associated signalling. In contrast, anthelmintic treatment was associated with coordinated inflammatory and endothelial activation, including cell adhesion molecule pathways, extracellular matrix remodelling, and transcriptional features consistent with active blood-brain barrier remodelling in a disrupted lesion state. Integrated pathway analysis showed that infection and treatment shared immune activation features but diverged in MAPK, vascular and endothelial programmes. These findings show that viable and post-treatment lesions are associated with distinct host transcriptional programmes involving immune regulation, endothelial activation and barrier-associated tissue remodelling. By defining these lesion-associated signatures, this study provides a framework for understanding parasite persistence, inflammation and disease progression in porcine neurocysticercosis.
2026-06-08 | GSE334289 | GEO