HCV data fitting
Ontology highlight
ABSTRACT:
SUBMITTER: 
Philip Aston
PROVIDER: MODEL1807030001 | BioModels | 2018-07-05
REPOSITORIES: BioModels
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| MODEL1807030001?filename=HCV%20data%20fitting.zip | Other |
Items per page: 5 1 - 1 of 1 |
Similar Datasets
Project description:Philip Aston. A New Model for the Dynamics of Hepatitis C Infection: Derivation, Analysis and Implications. Viruses 10, 4 (2018).
We review various existing models of hepatitis C virus (HCV) infection and show that there are inconsistencies between the models and known behaviour of the infection. A new model for HCV infection is proposed, based on various dynamical processes that occur during the infection that are described in the literature. This new model is analysed, and three steady state branches of solutions are found when there is no stem cell generation of hepatocytes. Unusually, the branch of infected solutions that connects the uninfected branch and the pure infection branch can be found analytically and always includes a limit point, subject to a few conditions on the parameters. When the action of stem cells is included, the bifurcation between the pure infection and infected branches unfolds, leaving a single branch of infected solutions. It is shown that this model can generate various viral load profiles that have been described in the literature, which is confirmed by fitting the model to four viral load datasets. Suggestions for possible changes in treatment are made based on the model.
2024-09-02 | BIOMD0000000713 | BioModels
Project description:Chronic viral hepatitis after infection with hepatotropic viruses like hepatitis B virus (HBV) affects 300 million persons worldwide, which as the result of chronic immune-mediated hepatic inflammation cause liver cirrhosis and cancer being responsible for 800.000 deaths per year3. Chronic viral hepatitis is maintained by failure of the host´s immune response to control viral infection, but the mechanisms for this inability of virus-specific CD8 T cells to eliminate HBV-infected hepatocytes remain unclear. Here, we demonstrate that during persistent experimental infection with hepatotropic viruses and HBV replication in hepatocytes all virus-specific CD8 T cells present in the liver expressed the tissue-residency markers CXCR6 and CD69. However, RNAseq analysis revealed that CXCR6+CD8 T cells during persistent hepatotropic infection were retained in the liver because of antigen-recognition rather than a transcriptional tissue-residency program, in contrast to canonical liver-resident memory CXCR6+CD8 T cells emerging after resolved infection. Whereas during persistent infection with a model virus like lymphocytic choriomeningitis virus with broad tissue and cell tropism exhausted CD8 T cells show graded loss of effector functions, hepatic virus-specific CXCR6+CD8 T cells during persistent infection with hepatotropic viruses were blinded and completely non-responsive to stimulation in absence of a canonical tox exhaustion signature. Rather, in blinded liver CXCR6+CD8 T cells, transcription factor network analysis revealed Crem, the cAMP-responsive-element-modulator, as the only transcription factor discreetly active in CD8 T cells with complete loss of effector function during persistent hepatotropic infection. Similarly, single cell RNA-sequencing of peripheral blood HBcore-specific CD8 T cells from chronic hepatitis B patients also revealed enhanced CREM activity. Notably, knock-out of the inhibitory CREM/ICER gene in T cells failed to rescue protective T cell immunity during persistent infection with hepatotropic viruses pointing towards post-translational mechanisms relevant for enhanced Crem activity and loss of effector function. Indeed, T cell receptor-associated signalling was blocked in blinded antigen-specific CXCR6+CD8 T cells, that in situ during persistent hepatotropic infection were in close proximity to liver sinusoidal endothelial cells producing high amounts of cAMP-inducing prostanoids. Inhibitory cAMP/PKA/CSK activity increased CREM activity and disconnected CXCR6+CD8 T cells from activation signalling through the T cell receptor. Thus, enhanced CREM expression identifies blinded liver CXCR6+CD8 T cells, but loss of effector functions is caused by post-translational prevention of signalling, which identifies novel molecular targets for immune monitoring and immune therapy of chronic hepatitis B.
2024-05-09 | GSE212925 | GEO
Project description:Hepatitis E virus (HEV) infection, one of the most common forms of hepatitis worldwide, is often associated with extrahepatic, particularly renal, manifestations. However, the underlying mechanisms are incompletely understood. Here, we report the development of a de novo immune complex-mediated glomerulonephritis (GN) in a kidney transplant recipient with chronic hepatitis E. Applying immunostaining, electron microscopy, and mass spectrometry after laser-capture microdissection, we show that GN developed in parallel with increasing glomerular deposition of a non-infectious, genome-free and non-glycosylated HEV open reading frame 2 (ORF2) capsid protein. No productive HEV infection of kidney cells is detected. Patients with acute hepatitis E display similar but less pronounced deposits. Our results establish a link between the production of HEV ORF2 protein and the development of hepatitis E-associated GN. The formation of glomerular IgG-HEV ORF2 immune complexes discovered here provides a mechanistic explanation of how the actually hepatotropic HEV can cause variable renal manifestations. These findings directly provide a tool for etiology-based diagnosis of hepatitis E-associated GN as a distinct entity and suggest therapeutic implications.
2025-01-18 | PXD055348 | Pride
Project description:This is an ordinary differential equation mathematical model investigating the early responses of human monocyte-derived dendritic cells to infection by two H1N1 influenza A viruses of different clinical outcomes: pandemic A/California/4/2009 and seasonal A/New Caledonia/20/1999.
2024-09-02 | BIOMD0000000889 | BioModels
Project description:The chimpanzee is the only model other than man for investigating the pathogenesis of viral hepatitis types A through E. Studies of the host response, including microarray analyses, have relied on the close relationship between these two primate species: chimpanzee samples are commonly tested with human-based reagents. In this study, the host response to two dissimilar viruses, hepatitis E virus (HEV) and hepatitis C virus (HCV), was compared in multiple experimentally-infected chimpanzees. Affymetrix U133+2.0 human microarray chips were used to assess the entire transcriptome in serial liver biopsies obtained over the course of the infections. The comparison utilized a permutational t-test-based analysis of selected time points. More specifically, baseline samples were compared with post-inoculation samples that were strategically chosen based on their relationship to viremia, and probe sequences were aligned to the human and chimpanzee genome sequences to assess their relative sensitivity for detecting differentially expressed genes. Regardless of the viral infection, the alignment of differentially expressed genes to the human genome sequence resulted in a larger number of genes being identified when compared with alignment to the chimpanzee genome sequence. This probably reflects the lesser refinement of gene annotation for chimpanzees. In general, the two viruses demonstrated very distinct temporal changes in host response genes, although both RNA viruses induced genes that were involved in many of the same biological systems, including interferon-induced genes. The host response to HCV infection was more robust than the response to HEV infection.
2010-09-22 | GSE22160 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE35462: Genome-wide analysis of histone methylation reveals chromatin state-based regulation of host cellular gene expression induced by hepatitis B viruses (ChIP-Seq dataset) GSE35464: Genome-wide analysis of histone methylation reveals chromatin state-based regulation of host cellular gene expression induced by hepatitis B viruses (DGE dataset) Refer to individual Series
2012-07-31 | E-GEOD-35465 | biostudies-arrayexpress
Project description:We use MeRIP-seq and PAR-CLIP in liver cell lines to detail the role of m6A in positive strand RNA virus infection. We find that hepatitis C virus, dengue virus, West Nile virus, yellow fever virus, and Zika virus all contain m6A within their genomes, with some conservation between viruses in methylation sites.
2016-10-21 | GSE83438 | GEO
Project description:Chronic hepatitis B, C and D virus (HBV, HCV, HDV) infections are leading causes of liver disease and cancer worldwide. Although these viruses differ markedly in their life cycle and genomic organization, they exclusively infect hepatocytes. Recently, the sodium taurocholate cotransporting polypeptide (NTCP) was identified as the first functional receptor for HBV and HDV. Here, we report that NTCP also facilitates HCV entry into human hepatocytes, by augmenting the bile acid-mediated repression of IFN-stimulated genes (ISGs), including IFITM2 and IFITM3, to increase the susceptibility of cells to HCV entry. Furthermore, an HBV-derived preS1 peptide, known to bind NTCP and to inhibit bile acid uptake and HBV infection, inhibits HCV entry by enhancing the expression of ISGs. Our study highlights NTCP as a novel player linking bile acid metabolism to the interferon response in hepatocytes and establishes a role for NTCP in the entry process of multiple hepatotropic viruses, via distinct mechanisms. Collectively, these findings enhance our understanding of hepatitis virus-host interactions and suggest NTCP as an attractive antiviral target for HBV/HCV co-infection. Transcriptome profiling by DNA microarray of Huh7.5.1 cells transduced to express NTCP.
2016-10-25 | E-GEOD-79089 | biostudies-arrayexpress
Project description:Fighting viral infections is hampered by the scarcity of viral targets and their variability resulting in development of resistance. Viruses depend on cellular molecules for their life cycle, which are attractive alternative targets, provided that they are dispensable for normal cell functions. Using the model organism Drosophila melanogaster, we identify the ribosomal protein RACK1 as a cellular factor required for infection by internal ribosome entry site (IRES)-containing viruses. We further show that RACK1 is an essential determinant for hepatitis C virus translation and infection indicating that its function is conserved among distantly related human and fly viruses. Inhibition of RACK1 does not affect Drosophila or human cell viability and proliferation, and RACK1-silenced adult flies are viable, indicating that this protein is not essential for general translation. Our findings demonstrate a specific function for RACK1 in selective mRNA translation and uncover a new target for the development of broad antiviral intervention. 4 Controls 4 RACK1 silenced cells
2015-05-14 | E-GEOD-60374 | biostudies-arrayexpress
Project description:Hepatitis B virus (HBV) infection could cause hepatitis, liver cirrhosis and hepatocellular carcinoma. HBV-mediated pathogenesis is only partially understood, but X protein (HBx) reportedly possesses oncogenic potential. Exosomes are small membrane vesicles with diverse functions released by various cells including hepatocytes, and HBV harnesses cellular exosome biogenesis and export machineries for virion morphogenesis and secretion. Therefore, HBV infection might cause changes in exosome contents with functional implications for both virus and host. In this project, exosome protein content changes induced by HBV and HBx were quantitatively analyzed by SILAC/LC-MS/MS. Exosomes prepared from SILAC-labeled hepatoma cell line Huh-7 transfected with HBx, wildtype or HBx-null HBV replicon plasmids were analyzed by LC-MS/MS.
2017-03-29 | MSV000080794 | MassIVE