ArticleNature genetics2013
A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus.
Article in Nature genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00341484 (Genetic Susceptibility to Oncogenic Viruses), which is not on this map. Cited by 525 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Genetic Susceptibility to Oncogenic Viruses
Who cites it
525 citing papers in PubMed, 1 synthesis or guideline pooled it, 916 citations in OpenAlex.
- Pooled it
- Peginterferon lambda for the treatment of outpatients with COVID-19: a phase 2, placebo-controlled randomised trial.The Lancet. Respiratory medicine · 2021Trial
- Germline genetic factors influence the outcome of interferon-α therapy in polycythemia vera.Blood · 2021Trial
- Role ofResearch square · 2026Article
- IFNλ4 Gene Variants Are Associated with CD8Biomolecules · 2026Article
- Pharmacogenomics of antibacterial and antiviral therapies: Clinical actionability, evidence gaps, and future directions.Pharmacological reviews · 2026Review
- Subtype-specific functions of basal IFNλs.Journal of virology · 2026Review
- Lineage-specific chromatin poising enforced by ETS-IRF composite elements determines the divergent interferon responses of plasmacytoid dendritic cells and epithelial cells.bioRxiv : the preprint server for biology · 2026Article
- Interferon lambda in anti-viral defense and cancer: dual roles, mechanism and therapeutic potential.Journal of translational medicine · 2026Review
- Targets of protective immunity and opportunities in hepatitis C virus vaccine development.Nature reviews. Immunology · 2026Review
- IFN-λ4 Exhibits Differential Induction and Antiviral Activity in RSV and HMPV Infections.Viruses · 2026Article
- Unraveling the Biology of Interferon-Stimulated Genes: Mechanisms, Functions, and Clinical Implications.Infection and drug resistance · 2026Review
- Cancer disparities: an extensive review.Ecancermedicalscience · 2026Review
- Basal IFNλ2/3 signaling is required for ISG expression and viral control in human intestinal epithelial cells.PLoS pathogens · 2026Article
- Zika Virus: A Tale of Two Lineages.Pathogens (Basel, Switzerland) · 2025Review
- Hepatitis C virus modifiedJournal of virology · 2025Article
- Basal IFN-λ2/3 expression mediates tight junction formation in human epithelial cells.The EMBO journal · 2025Article
- Association of IFNL4 and IFITM3 Genetic Variants with Susceptibility to HCV-Related Liver Cirrhosis and Hepatocellular Carcinoma.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- Sex based relative expression of estrogen receptors and tumor necrosis factor-alpha in liver affects hepatitis C virus viral pathogenesis.World journal of gastroenterology · 2025Article
- Interferons in health and disease.Cell · 2025Review
465 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
24 authors at 10 institutions in 1 country.
Funding
Abstract
Chronic infection with hepatitis C virus (HCV) is a common cause of liver cirrhosis and cancer. We performed RNA sequencing in primary human hepatocytes activated with synthetic double-stranded RNA to mimic HCV infection. Upstream of IFNL3 (IL28B) on chromosome 19q13.13, we discovered a new transiently induced region that harbors a dinucleotide variant ss469415590 (TT or ΔG), which is in high linkage disequilibrium with rs12979860, a genetic marker strongly associated with HCV clearance. ss469415590[ΔG] is a frameshift variant that creates a novel gene, designated IFNL4, encoding the interferon-λ4 protein (IFNL4), which is moderately similar to IFNL3. Compared to rs12979860, ss469415590 is more strongly associated with HCV clearance in individuals of African ancestry, although it provides comparable information in Europeans and Asians. Transient overexpression of IFNL4 in a hepatoma cell line induced STAT1 and STAT2 phosphorylation and the expression of interferon-stimulated genes. Our findings provide new insights into the genetic regulation of HCV clearance and its clinical management.
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What OpenQuestion holds
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.