ArticleMolecular and cellular biology2006
Inquiring into the differential action of interferons (IFNs): an IFN-alpha2 mutant with enhanced affinity to IFNAR1 is functionally similar to IFN-beta.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
127 citing papers in PubMed.
- A trial of intrapleural adenoviral-mediated Interferon-α2b gene transfer for malignant pleural mesothelioma.American journal of respiratory and critical care medicine · 2011Trial
- Interferon-α and -β subtypes have temporally distinct roles in containing viral spread and protecting vital organs.Research square · 2026Article
- A modular platform for Sterically Masked Activated Cytokines (SMACks).Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Interferon-Based Therapeutics in Cancer Therapy: Past, Present, and Future.International journal of molecular sciences · 2025Review
- Receptor dimerization enables ligand discrimination through tunable response heterogeneity.PLoS computational biology · 2025Article
- Engineering non-pathogenic bacteria for auto-transporter-driven secretion of functional interferon.Gut microbes · 2025Article
- Interferon-induced protein ISG15 in the central nervous system, quo vadis?FEBS letters · 2025Review
- Type I IFNs enhance human dorsal root ganglion nociceptor excitability and induce TRPV1 sensitization.JCI insight · 2025Article
- Highly suitable LFBK cells for African swine fever virus replication and type I interferon-induced immune studies.Veterinary research · 2025Article
- Implications of glycosylation for the development of selected cytokines and their derivatives for medical use.Biotechnology advances · 2024Review
- Macrophages treated with interferons induce different responses in lymphocytes via extracellular vesicles.iScience · 2024Article
- Mechanism of action and treatment of type I interferon in hepatocellular carcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Review
- HIV-1 Infection Results in Sphingosine-1-Phosphate Receptor 1 Dysregulation in the Human Thymus.International journal of molecular sciences · 2023Article
- Molecular and cellular factors determining the functional pleiotropy of cytokines.The FEBS journal · 2023Review
- STAM and Hrs interact sequentially with IFN-α Receptor to control spatiotemporal JAK-STAT endosomal activation.Nature cell biology · 2023Article
- Emerging principles of cytokine pharmacology and therapeutics.Nature reviews. Drug discovery · 2023Review
- Antiviral Effect of pIFNLs against PEDV and VSV Infection in Different Cells.International journal of molecular sciences · 2022Article
- Deciphering signal transduction networks in the liver by mechanistic mathematical modelling.The Biochemical journal · 2022Article
- Life-threatening viral disease in a novel form of autosomal recessive IFNAR2 deficiency in the Arctic.The Journal of experimental medicine · 2022Article
- The use of supercytokines, immunocytokines, engager cytokines, and other synthetic cytokines in immunotherapy.Cellular & molecular immunology · 2022Review
67 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alpha and beta interferons (IFN-alpha and IFN-beta) are multifunctional cytokines that exhibit differential activities through a common receptor composed of the subunits IFNAR1 and IFNAR2. Here we combined biophysical and functional studies to explore the mechanism that allows the alpha and beta IFNs to act differentially. For this purpose, we have engineered an IFN-alpha2 triple mutant termed the HEQ mutant that mimics the biological properties of IFN-beta. Compared to wild-type (wt) IFN-alpha2, the HEQ mutant confers a 30-fold higher binding affinity towards IFNAR1, comparable to that measured for IFN-beta, resulting in a much higher stability of the ternary complex as measured on model membranes. The HEQ mutant, like IFN-beta, promotes a differentially higher antiproliferative effect than antiviral activity. Both bring on a down-regulation of the IFNAR2 receptor upon induction, confirming an increased ternary complex stability of the plasma membrane. Oligonucleotide microarray experiments showed similar gene transcription profiles induced by the HEQ mutant and IFN-beta and higher levels of gene induction or repression than those for wt IFN-alpha2. Thus, we show that the differential activities of IFN-beta are directly related to the binding affinity for IFNAR1. Conservation of the residues mutated in the HEQ mutant within IFN-alpha subtypes suggests that IFN-alpha has evolved to bind IFNAR1 weakly, apparently to sustain differential levels of biological activities compared to those induced by IFN-beta.
Indexed as
Identifiers
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.