ArticleScientific reports2016
Convergent Transcription of Interferon-stimulated Genes by TNF-α and IFN-α Augments Antiviral Activity against HCV and HEV.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 57 citations in OpenAlex.
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- Host mature tRNAome as a decoding switch regulates antiviral and proviral responses.Nature communications · 2026Article
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- Single-cell heterogeneity in interferon induction potential is heritable and governed by variation in cell state.bioRxiv : the preprint server for biology · 2025Article
- Mammalian innate antiviral defenses: beyond interferon.Journal of virology · 2025Review
- ISG20 RestrictsMicroorganisms · 2025Article
- Elevated serum interferon-α2 associates with activity and flare risk in juvenile-onset systemic lupus erythematosus.Rheumatology (Oxford, England) · 2025Article
- Plasmacytoid dendritic cell sensing of hepatitis E virus is shaped by both viral and host factors.Life science alliance · 2025Article
- Spatial enrichment of the type 1 interferon signature in the brain of a neuropsychiatric lupus murine model.Brain, behavior, and immunity · 2023Article
- Serum IFNα2 levels are associated with disease activity and outperform IFN-I gene signature in a longitudinal childhood-onset SLE cohort.Rheumatology (Oxford, England) · 2023Article
- Rotavirus Infection in Swine: Genotypic Diversity, Immune Responses, and Role of Gut Microbiome in Rotavirus Immunity.Pathogens (Basel, Switzerland) · 2022Review
- 17β-Oestradiol Protects from Hepatitis C Virus Infection through Induction of Type I Interferon.Viruses · 2022Article
- Serum interferon-α2 measured by single-molecule array associates with systemic disease manifestations in Sjögren's syndrome.Rheumatology (Oxford, England) · 2022Article
- Similarities, differences, and possible interactions between hepatitis E and hepatitis C viruses: Relevance for research and clinical practice.World journal of gastroenterology · 2022Review
- The Antiviral Effects of Jasminin via Endogenous TNF-α and the Underlying TNF-α-Inducing Action.Molecules (Basel, Switzerland) · 2022Article
- Manipulation of innate immune signaling pathways by SARS-CoV-2 non-structural proteins.Frontiers in microbiology · 2022Article
- Immune Mechanisms Underlying Hepatitis B Surface Antigen Seroclearance in Chronic Hepatitis B Patients With Viral Coinfection.Frontiers in immunology · 2022Review
- TRIMs: selective recruitment at different steps of the NF-κB pathway-determinant of activation or resolution of inflammation.Cellular and molecular life sciences : CMLS · 2021Review
- Interplay between Hepatitis E Virus and Host Cell Pattern Recognition Receptors.International journal of molecular sciences · 2021Review
- Merkel Cell Polyomavirus Infection Induces an Antiviral Innate Immune Response in Human Dermal Fibroblasts.Journal of virology · 2021Article
Corrections and comments
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Authors and funding
16 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
IFN-α has been used for decades to treat chronic hepatitis B and C, and as an off-label treatment for some cases of hepatitis E virus (HEV) infection. TNF-α is another important cytokine involved in inflammatory disease, which can interact with interferon signaling. Because interferon-stimulated genes (ISGs) are the ultimate antiviral effectors of the interferon signaling, this study aimed to understand the regulation of ISG transcription and the antiviral activity by IFN-α and TNF-α. In this study, treatment of TNF-α inhibited replication of HCV by 71 ± 2.4% and HEV by 41 ± 4.9%. Interestingly, TNF-α induced the expression of a panel of antiviral ISGs (2-11 fold). Blocking the TNF-α signaling by Humira abrogated ISG induction and its antiviral activity. Chip-seq data analysis and mutagenesis assay further revealed that the NF-κB protein complex, a key downstream element of TNF-α signaling, directly binds to the ISRE motif in the ISG promoters and thereby drives their transcription. This process is independent of interferons and JAK-STAT cascade. Importantly, when combined with IFN-α, TNF-α works cooperatively on ISG induction, explaining their additive antiviral effects. Thus, our study reveals a novel mechanism of convergent transcription of ISGs by TNF-α and IFN-α, which augments their antiviral activity against HCV and HEV.
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