ArticleProceedings of the National Academy of Sciences of the United States of America2015
Roles of unphosphorylated ISGF3 in HCV infection and interferon responsiveness.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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55 citing papers in PubMed, 88 citations in OpenAlex.
- Review
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- Interferon signaling pathways in health and disease.Molecular biomedicine · 2025Review
- Context-dependent impact of type I interferon signaling in cancer.Molecular cancer · 2025Review
- Identification of AMOTL2 as an antiviral factor that enhances the human type I interferon response against Zika virus.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Hepatitis E virus: from innate sensing to adaptive immune responses.Nature reviews. Gastroenterology & hepatology · 2024Review
- Machine learning model reveals roles of interferon‑stimulated genes in sorafenib‑resistant liver cancer.Oncology letters · 2024Article
- Dynamic control of gene expression by ISGF3 and IRF1 during IFNβ and IFNγ signaling.The EMBO journal · 2024Article
- Ruxolitinib Improves Immune-Dysregulation Features but not Epigenetic Abnormality in a Patient with STAT1 GOF.Journal of clinical immunology · 2024Article
- Respiratory syncytial virus NS1 inhibits anti-viral Interferon-α-induced JAK/STAT signaling, by limiting the nuclear translocation of STAT1.Frontiers in immunology · 2024Article
- Interferon lambda in respiratory viral infection: immunomodulatory functions and antiviral effects in epithelium.Frontiers in immunology · 2024Review
- Roles of ubiquitin-specific proteases in inflammatory diseases.Frontiers in immunology · 2024Review
- ISGF3 and STAT2/IRF9 Control Basal and IFN-Induced Transcription through Genome-Wide Binding of Phosphorylated and Unphosphorylated Complexes to Common ISRE-Containing ISGs.International journal of molecular sciences · 2023Article
- Article
- Corticosteroids reduce pathologic interferon responses by downregulating STAT1 in patients with high-risk COVID-19.Experimental & molecular medicine · 2023Article
- Crosstalk between tumor-associated macrophages and neighboring cells in hepatocellular carcinoma.Clinical and molecular hepatology · 2022Review
- Intrahepatic inflammatory IgAJournal for immunotherapy of cancer · 2022Article
- The TRRAP transcription cofactor represses interferon-stimulated genes in colorectal cancer cells.eLife · 2022Article
- Mechanisms of Viral Degradation of Cellular Signal Transducer and Activator of Transcription 2.International journal of molecular sciences · 2022Review
- PD-L1 sustains chronic, cancer cell-intrinsic responses to type I interferon, enhancing resistance to DNA damage.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Up-regulation of IFN-stimulated genes (ISGs) is sustained in hepatitis C virus (HCV)-infected livers. Here, we investigated the mechanism of prolonged ISG expression and its role in IFN responsiveness during HCV infection in relation to unphosphorylated IFN-stimulated gene factor 3 (U-ISGF3), recently identified as a tripartite transcription factor formed by high levels of IFN response factor 9 (IRF9), STAT1, and STAT2 without tyrosine phosphorylation of the STATs. The level of U-ISGF3, but not tyrosine phosphorylated STAT1, is significantly elevated in response to IFN-λ and IFN-β during chronic HCV infection. U-ISGF3 prolongs the expression of a subset of ISGs and restricts HCV chronic replication. However, paradoxically, high levels of U-ISGF3 also confer unresponsiveness to IFN-α therapy. As a mechanism of U-ISGF3-induced resistance to IFN-α, we found that ISG15, a U-ISGF3-induced protein, sustains the abundance of ubiquitin-specific protease 18 (USP18), a negative regulator of IFN signaling. Our data demonstrate that U-ISGF3 induced by IFN-λs and -β drives prolonged expression of a set of ISGs, leading to chronic activation of innate responses and conferring a lack of response to IFN-α in HCV-infected liver.
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