ArticleJournal of gastroenterology2009
Interferon-alpha-induced mTOR activation is an anti-hepatitis C virus signal via the phosphatidylinositol 3-kinase-Akt-independent pathway.
Article in Journal of gastroenterology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- The crucial regulatory role of type I interferon in inflammatory diseases.Cell & bioscience · 2023Review
- IFNs Reset the Differential Capacity of Human Monocyte Subsets to Produce IL-12 in Response to Microbial Stimulation.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- L-Leucine Promotes STAT1 and ISGs Expression in TGEV-Infected IPEC-J2 CellsFrontiers in immunology · 2021Article
- IFNα Impairs Autophagic Degradation of mtDNA Promoting Autoreactivity of SLE Monocytes in a STING-Dependent Fashion.Cell reports · 2018Article
- Pegylated IFN-α suppresses hepatitis C virus by promoting the DAPK-mTOR pathway.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Interferon receptor signaling in malignancy: a network of cellular pathways defining biological outcomes.Molecular cancer research : MCR · 2014Review
- Hepatitis C virus reactivation in cancer patients in the era of targeted therapies.World journal of gastroenterology · 2014Review
- Regulation of interferon-dependent mRNA translation of target genes.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2014Review
- Beta interferon regulation of glucose metabolism is PI3K/Akt dependent and important for antiviral activity against coxsackievirus B3.Journal of virology · 2014Article
- Modulation of PI3K-LXRα-dependent lipogenesis mediated by oxidative/nitrosative stress contributes to inhibition of HCV replication by quercetin.Laboratory investigation; a journal of technical methods and pathology · 2014Article
- Article
- Curing a viral infection by targeting the host: the example of cyclophilin inhibitors.Antiviral research · 2013Review
- Geranylgeranylacetone has anti-hepatitis C virus activity via activation of mTOR in human hepatoma cells.Journal of gastroenterology · 2012Article
- Immunomodulatory functions of type I interferons.Nature reviews. Immunology · 2012Review
- Temsirolimus in combination with carboplatin and paclitaxel in patients with advanced solid tumors: a NCIC-CTG, phase I, open-label dose-escalation study (IND 179).Annals of oncology : official journal of the European Society for Medical Oncology · 2012Article
- IL-29 and IFN-α regulate the expression of MxA, 2',5'-OAS and PKR genes in association with the activation of Raf-MEK-ERK and PI3K-AKT signal pathways in HepG2.2.15 cells.Molecular biology reports · 2011Article
- Potential use of rapamycin in HIV infection.British journal of clinical pharmacology · 2010Review
- Lewis y antigen promotes the proliferation of ovarian carcinoma-derived RMG-I cells through the PI3K/Akt signaling pathway.Journal of experimental & clinical cancer research : CR · 2009Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectThe interferon-induced Jak-STAT signal alone is not sufficient to explain all the biological effects of IFN. The PI3-K pathways have emerged as a critical additional component of IFN-induced signaling. This study attempted to clarify that relationship between IFN-induced PI3-K-Akt-mTOR activity and anti-viral action.
resultWhen the human normal hepatocyte derived cell line was treated with rapamycin (rapa) before accretion of IFN-alpha, tyrosine phosphorylation of STAT-1 was diminished. Pretreatment of rapa had an inhibitory effect on the IFN-alpha-induced expression of PKR and p48 in a dose dependent manner. Rapa inhibited the IFN-alpha inducible IFN-stimulated regulatory element luciferase activity in a dose-dependent manner. However, wortmannin, LY294002 and Akt inhibitor did not influence IFN-alpha inducible luciferase activity. To examine the effect of PI3-K-Akt-mTOR on the anti-HCV action of IFN-alpha, the full-length HCV replication system, OR6 cells were used. The pretreatment of rapa attenuated its anti-HCV replication effect in comparison to IFN-alpha alone, whereas the pretreatment with PI3-K inhibitors, wortmannin and LY294002 and Akt inhibitor did not influence IFN-induced anti-HCV replication.
conclusionIFN-induced mTOR activity, independent of PI3K and Akt, is the critical factor for its anti-HCV activity. Jak independent mTOR activity involved STAT-1 phosphorylation and nuclear location, and then PKR is expressed in hepatocytes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.