Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA111329 | ENA |
REPOSITORIES: ENA
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Project description:Hepatitis C virus (HCV) infection is a global health problem. A number of studies have implicated a direct role of cellular lipid metabolism in the HCV life cycle and inhibitors of the mevalonate pathway have been demonstrated to result in an antiviral state within the host cell. Transcriptome profiling was also conducted on Huh-7 human hepatoma cells bearing subgenomic HCV replicons with and without treatment with 25-hydroxycholesterol (25-HC), an inhibitor of the mevalonate pathway that alters lipid metabolism, to assess metabolic determinants of pro- and antiviral states within the host cell. Experiment Overall Design: compound treatment and time course
2009-01-02 | E-GEOD-14204 | biostudies-arrayexpress
Project description:Hepatitis C virus (HCV) infection is a global health problem. A number of studies have implicated a direct role of cellular lipid metabolism in the HCV life cycle and inhibitors of the mevalonate pathway have been demonstrated to result in an antiviral state within the host cell. Transcriptome profiling was also conducted on Huh-7 human hepatoma cells bearing subgenomic HCV replicons with and without treatment with 25-hydroxycholesterol (25-HC), an inhibitor of the mevalonate pathway that alters lipid metabolism, to assess metabolic determinants of pro- and antiviral states within the host cell. Keywords: treatment and time course
2008-12-25 | GSE14204 | GEO
Project description:Our work demonstrated that 25-hydroxycholesterol induces the expression of miR-185, a microRNA which reinforces the oxysterol's antiviral effects on hepatic metabolism. We used microarrays to detail the effect of miR-185 on hepatic gene expression, and, within repressed genes, identified an enrichment for genes associated with cholesterol biosynthesis.
2015-10-19 | GSE73165 | GEO
Project description:Physicochemical properties and composition of cellular membranes are crucial for regulating broad cellular responses including signaling and defense against pathogens. Dengue virus (DENV) exploits cholesterol-rich membranes and host lipid pathways, such as cholesterol biosynthesis, lipid raft organization, and lipid droplet formation, for entry, replication, and assembly. Additionally, lipid-based plasma membrane signaling can trigger innate immune responses that attenuate viral growth, underscoring the dual role of lipids in facilitating and restricting DENV infection. Here, we demonstrate that 25-hydroxycholesterol (25-HC), an oxidized cholesterol metabolite, inhibits DENV infection through a multifaceted mechanism. 25-HC disrupts viral membrane fusion by altering cholesterol distribution and lipid raft organization, impairing the binding and fusion of the DENV envelope (E) protein with host membranes. Additionally, 25-HC modulates host cholesterol metabolism by suppressing biosynthesis pathways essential for viral replication while enhancing lipid droplet formation and stress-response pathways. Transcriptomic analyses reveal that 25-HC primes innate immune responses, activating pro-inflammatory pathways such as the NLRP3 inflammasome and MAPK signaling, while selectively modulating interferon-stimulated gene expression. Notably, 25-HC exhibits synergistic antiviral effects when combined with direct-acting antivirals like Remdesivir, underscoring its potential in combination therapies. These findings establish 25-HC as a promising candidate for host-directed antiviral strategies against DENV and other enveloped viruses.
2026-04-07 | GSE307959 | GEO
Project description:Transcriptional profiling provides global snapshots of virus-mediated cellular reprogramming, which can simultaneously encompass pro- and antiviral components. To determine early transcriptional signatures associated with HCV infection of authentic target cells, we performed ex vivo infections of adult primary human hepatocytes (PHHs) from seven donors. Coordinated sampling identified minimal gene dysregulation at six hours post infection (hpi) in PHHs. In contrast, at 72 hpi, massive increases in the breadth and magnitude of HCV-induced gene dysregulation were apparent, affecting gene classes associated with diverse biological processes. Comparison with HCV-induced transcriptional dysregulation in Huh-7.5 cells identified limited overlap between the two systems. Of note, in PHHs, HCV infection initiated broad upregulation of canonical interferon (IFN)-mediated defense programs, limiting viral RNA replication and abrogating virion release. In addition, we confirm that constitutive expression of IRF1 in PHHs maintains a steady-state antiviral program in the absence of infection which can further reduce HCV RNA replication. We also detected infection-induced signatures of translational shutoff in PHHs - downregulation of ~90 genes encoding components of the EIF2 translation initiation complex and ribosomal subunits. As HCV polyprotein translation occurs independently of the EIF2 complex, this process is pro-viral: only translation initiation of host transcripts is arrested. The combination of antiviral intrinsic and inducible immunity, balanced against pro-viral programs, including translational arrest, maintains HCV replication at a low-level in PHHs. This may ultimately keep HCV under the radar of extra-hepatocyte immune surveillance while initial infection is established, promoting tolerance, preventing clearance and facilitating progression to chronicity.
2021-03-02 | GSE166428 | GEO
Project description:Hepatitis C virus (HCV) infection is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. HCV can be sensed by host innate immunity to induce expression of interferons (IFNs) and a number of antiviral effectors. HCV-encoded NS3/4 serine protease can subvert host innate immune responses by cleaving MAVS, a critical adaptor protein in the RLR-mediated IFN signaling. To study innate immunity in the context of HCV infection, we constructed Huh7-MAVSR cells which express a mutant MAVS resistant to NS3/4A cleavage. HCV infection induces robust IFN response in Huh7-MAVSR cells, providing a cellular system to study antiviral innate immune response against HCV infection. To analyze host innate antiviral effectors against HCV infection, we performed an mRNA microarray analysis in the HCV-infected Huh7-MAVSR cells.
2018-02-08 | GSE110312 | GEO
Project description:Background/Aim: Legalon SIL (SIL) is a chemically hydrophilized version of silibinin that has exhibited hepatoprotective and antiviral effectiveness against hepatitis C virus (HCV) in patients leading to viral clearance in combination with ribavirin. To elucidate the incompletely understood mode of action of SIL against HCV, we studied viral response kinetics and cellular gene expression during SIL treatment in the absence of an adaptive immune response in uPA-SCID chimeric mice with humanized livers. Methods: Chronically HCV-infected mice were treated with daily intravenous SIL at 469 mg/kg (n=5), 265 mg/kg (n=5) or 61.5 mg/kg (n=5). Serum HCV and human albumin (hAlb) were measured frequently and liver HCV RNA was analyzed at days 3 and 14. Microarray analysis of human hepatocyte gene expression was performed at days 0, 3, and 14 of treatment. Mathematical modeling was used to estimate viral kinetic parameters and SIL effectiveness. Results: While hAlb remained constant, a biphasic viral decline in serum was observed consisting of a rapid 1st phase followed by a 2nd slower (or plateau with the two lower SIL dosing) phase. SIL effectiveness in blocking viral production was similar among dosing groups (median =77%). However, the rate of HCV-infected hepatocyte decline, δ, was dose-dependent. Intracellular HCV RNA levels correlated (r=0.66, P=.01) with serum HCV RNA. Pathway analysis revealed increased anti-inflammatory and anti-proliferative gene expression in human hepatocytes in SIL-treated mice. Conclusions: The results suggest that SIL could lead to a continuous 2nd phase viral decline, i.e., potentially viral clearance, in the absence of adaptive immune response along with increased anti-inflammatory and anti-proliferative gene expression in human hepatocytes.
2017-04-01 | GSE79103 | GEO
Project description:Hepatitis C virus (HCV) infection constitutes a global health problem with 71 million people currently chronically infected. Recent studies have reported that C19orf66 is expressed as an interferon (IFN)-stimulated gene; however, the intrinsic regulation of this gene within the liver as well as its antiviral effects against HCV remains elusive. In this study, we observed an upregulation of C19orf66 in vivo and ex vivo in response to HCV infection and to IFN therapy. Expression of C19orf66 restricted HCV infection, whereas CRIPSPR/Cas9 mediated knockout of C19orf66 attenuated IFN-mediated suppression of HCV replication. Co-immunoprecipitation followed by mass spectrometry identified a stress granule dominated interactome of C19orf66. Mechanistic studies revealed that C19orf66 expression impairs HCV-induced elevation of PI(4)P and alters the morphology of the viral replication organelle, designated membranous web, thus suppressing viral RNA replication. Collectively, our data suggest that C19orf66 contributes to the innate immune response against HCV in the liver.
2020-02-28 | GSE146075 | GEO
Project description:Host cells harbor various intrinsic mechanisms to restrict viral infections as a first line of antiviral defense. Viruses have evolved various countermeasures against these antiviral mechanisms. Here we show that N-Myc Downstream-Reguated Gene 1 (NDRG1) limits productive HCV infection by inhibiting viral assembly. Interestingly, HCV infection down-regulates NDRG1 protein and mRNA expression. Loss of NDRG1 increases the size and number of lipid droplets, which are the sites of HCV assembly. HCV suppresses NDRG1 expression by up-regulating MYC, which directly inhibits the transcription of NDRG1. Up-regulation of MYC also leads to reduced expression of NDRG1-specific kinase SGK1, resulting in markedly diminished phosphorylation of NDRG1. Knockdown of MYC during HCV infection rescues NDRG1 expression and phosphorylation, suggesting that MYC regulates NDRG1 at both transcriptional and post-translational levels. Overall, our results suggest that NDRG1 restricts HCV assembly by limiting lipid droplet formation. HCV counteracts this intrinsic antiviral mechanism by down-regulating NDRG1 via a MYC-dependent mechanism.
2017-11-17 | GSE106988 | GEO
Project description:Previous studies have demonstrated that 25-hydroxycholesterol (25HC), which is involved in the initiation and progression of osteoarthritis (OA), can be sulfated by SULT2B1 to produce 25-hydroxycholesterol-3-sulfate (25HC3S). Given this background, this study aims to investigate whether 25HC3S and 25HC have different functional effects on articular chondrocytes. Additionally, since 25HC has been proven to be an endogenous ligand of liver X receptor (LXR), this study also compares the effects elicited by the LXR agonist GW3965 on articular chondrocytes to provide insights into whether 25HC and its sulfated derivative, 25HC3S, exert distinct influences on the LXR signaling pathway.
2026-04-21 | GSE283360 | GEO