ArticleThe Journal of clinical investigation2014
Pegylated IFN-α regulates hepatic gene expression through transient Jak/STAT activation.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 47 citations in OpenAlex.
- Cloning and Functional Characterization of Novel Human Neutralizing Anti-IFN-α and Anti-IFN-β Antibodies.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Molecular evolution and expression patterns of myxovirus resistance proteins inActa biochimica et biophysica Sinica · 2024Article
- Review
- Interferon Signaling-Dependent Contribution of Glycolysis to Rubella Virus Infection.Pathogens (Basel, Switzerland) · 2022Article
- Article
- Intracellular interferon signalling pathways as potential regulators of covalently closed circular DNA in the treatment of chronic hepatitis B.World journal of gastroenterology · 2021Review
- Restoration of type I interferon signaling in intrahepatically primed CD8+ T cells promotes functional differentiation.JCI insight · 2021Article
- Disentangling molecular mechanisms regulating sensitization of interferon alpha signal transduction.Molecular systems biology · 2020Article
- Relationships Between Vitamin D Status and Cytokine: Results from Interferon-Based Therapy in Non-Cirrhotic, Treatment-Naïve Patients with Chronic Hepatitis C Infection.Journal of inflammation research · 2020Article
- Liver transcriptome profiling of beef steers with divergent growth rate, feed intake, or metabolic body weight phenotypes1.Journal of animal science · 2019Article
- PSTPIP2 connects DNA methylation to macrophage polarization in CCL4-induced mouse model of hepatic fibrosis.Oncogene · 2018Article
- Constitutive Interferon Maintains GBP Expression Required for Release of Bacterial Components Upstream of Pyroptosis and Anti-DNA Responses.Cell reports · 2018Article
- Macrophage-Derived Extracellular Vesicles Induce Long-Lasting Immunity Against Hepatitis C Virus Which Is Blunted by Polyunsaturated Fatty Acids.Frontiers in immunology · 2018Article
- SOCS1 is an inducible negative regulator of interferon λ (IFN-λ)-induced gene expressionThe Journal of biological chemistry · 2017Article
- Persistent Loss of Hepatitis B Virus Markers in Serum without Cellular Immunity by Combination of Peginterferon and Entecavir Therapy in Humanized Mice.Antimicrobial agents and chemotherapy · 2017Article
- Transcriptional response to hepatitis C virus infection and interferon-alpha treatment in the human liver.EMBO molecular medicine · 2017Article
- Article
- Improved Survival Among all Interferon-α-Treated Patients in HCV-002, a Veterans Affairs Hepatitis C Cohort of 2211 Patients, Despite Increased Cirrhosis Among Nonresponders.Digestive diseases and sciences · 2016Article
- Suppression of USP18 Potentiates the Anti-HBV Activity of Interferon Alpha in HepG2.2.15 Cells via JAK/STAT Signaling.PloS one · 2016Article
- Hepatitis B virus spliced variants are associated with an impaired response to interferon therapy.Scientific reports · 2015Article
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The use of pegylated interferon-α (pegIFN-α) has replaced unmodified recombinant IFN-α for the treatment of chronic viral hepatitis. While the superior antiviral efficacy of pegIFN-α is generally attributed to improved pharmacokinetic properties, the pharmacodynamic effects of pegIFN-α in the liver have not been studied. Here, we analyzed pegIFN-α-induced signaling and gene regulation in paired liver biopsies obtained prior to treatment and during the first week following pegIFN-α injection in 18 patients with chronic hepatitis C. Despite sustained high concentrations of pegIFN-α in serum, the Jak/STAT pathway was activated in hepatocytes only on the first day after pegIFN-α administration. Evaluation of liver biopsies revealed that pegIFN-α induces hundreds of genes that can be classified into four clusters based on different temporal expression profiles. In all clusters, gene transcription was mainly driven by IFN-stimulated gene factor 3 (ISGF3). Compared with conventional IFN-α therapy, pegIFN-α induced a broader spectrum of gene expression, including many genes involved in cellular immunity. IFN-induced secondary transcription factors did not result in additional waves of gene expression. Our data indicate that the superior antiviral efficacy of pegIFN-α is not the result of prolonged Jak/STAT pathway activation in hepatocytes, but rather is due to induction of additional genes that are involved in cellular immune responses.
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