ArticleProceedings of the National Academy of Sciences of the United States of America2022
Differential interferon-α subtype induced immune signatures are associated with suppression of SARS-CoV-2 infection.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Long-Term Complications of Multisystem Inflammatory Syndrome in Children and Adults Post-COVID-19: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Cytokine levels associated with favorable clinical outcome in the CAPSID randomized trial of convalescent plasma in patients with severe COVID-19.Frontiers in immunology · 2022Trial
- Comparative innate immune responses across major RNA and DNA viral infections: Mechanisms, immunopathology, and therapeutic perspectives.Human vaccines & immunotherapeutics · 2026Review
- Current progress and role of lncRNAs in HBV infection and progression of hepatocellular carcinoma.Genes & diseases · 2026Review
- Article
- Single-cell analysis of signalling and transcriptional responses to type I interferons.EMBO reports · 2026Article
- Interferon-β Modulates Early Viral Replication Kinetics and Innate Responses to Non-Fatal Alphavirus Encephalomyelitis.Pathogens (Basel, Switzerland) · 2026Article
- Interferon-α and -β subtypes have temporally distinct roles in containing viral spread and protecting vital organs.Research square · 2026Article
- Interferon-induced immune signatures are associated with suppression of HEV infection in porcine cell culture models.Emerging microbes & infections · 2025Article
- Multimodal characterization of the responsiveness of eight hepatitis D virus genotype isolates to interferon-alpha treatment.Journal of virology · 2025Article
- Review
- Article
- Engineered RNA-based activation system for coronavirus sensing in live cells.Biodesign research · 2025Article
- PUM2 binds SARS-CoV-2 RNA and PUM1 mildly reduces viral RNA levels, but neither protein affects progeny virus production.The Journal of general virology · 2025Article
- Mycophenolic acid treatment drives the emergence of novel SARS-CoV-2 variants.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- An atlas of protein phosphorylation dynamics during interferon signaling.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Effect of prone positioning on inflammatory markers in blood and lungs: a retrospective cohort study in COVID-19-related ARDS.Frontiers in cellular and infection microbiology · 2025Article
- An extracellular humanized IFNAR immunocompetent mouse model for analyses of human interferon alpha and subtypes.Emerging microbes & infections · 2024Article
- The Antiviral Effects of Heat-KilledMicroorganisms · 2024Article
- Transient anti-interferon autoantibodies in the airways are associated with recovery from COVID-19.Science translational medicine · 2024Article
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Authors and funding
32 authors at 11 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type I interferons (IFN-I) exert pleiotropic biological effects during viral infections, balancing virus control versus immune-mediated pathologies, and have been successfully employed for the treatment of viral diseases. Humans express 12 IFN-alpha (α) subtypes, which activate downstream signaling cascades and result in distinct patterns of immune responses and differential antiviral responses. Inborn errors in IFN-I immunity and the presence of anti-IFN autoantibodies account for very severe courses of COVID-19; therefore, early administration of IFN-I may be protective against life-threatening disease. Here we comprehensively analyzed the antiviral activity of all IFNα subtypes against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to identify the underlying immune signatures and explore their therapeutic potential. Prophylaxis of primary human airway epithelial cells (hAEC) with different IFNα subtypes during SARS-CoV-2 infection uncovered distinct functional classes with high, intermediate, and low antiviral IFNs. In particular, IFNα5 showed superior antiviral activity against SARS-CoV-2 infection in vitro and in SARS-CoV-2-infected mice in vivo. Dose dependency studies further displayed additive effects upon coadministration with the broad antiviral drug remdesivir in cell culture. Transcriptomic analysis of IFN-treated hAEC revealed different transcriptional signatures, uncovering distinct, intersecting, and prototypical genes of individual IFNα subtypes. Global proteomic analyses systematically assessed the abundance of specific antiviral key effector molecules which are involved in IFN-I signaling pathways, negative regulation of viral processes, and immune effector processes for the potent antiviral IFNα5. Taken together, our data provide a systemic, multimodular definition of antiviral host responses mediated by defined IFN-I. This knowledge will support the development of novel therapeutic approaches against SARS-CoV-2.
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