ArticleThe Journal of clinical investigation2019
IFN-I response timing relative to virus replication determines MERS coronavirus infection outcomes.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 365 papers, 2 of them syntheses that pooled it.
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
365 citing papers in PubMed, 2 syntheses or guidelines pooled it, 587 citations in OpenAlex.
- JAK inhibitors and COVID-19.Journal for immunotherapy of cancer · 2022Pooled it
- Janus kinases inhibitors for coronavirus disease-2019: A pairwise and Bayesian network meta-analysis.Frontiers in medicine · 2022Pooled it
- Effect of inhaled interferon-β1a on SARS-CoV-2 diversity and evolution.Microbiology spectrum · 2026Trial
- Type I interferon autoantibodies in hospitalized patients with Middle East respiratory syndrome and association with outcomes and treatment effect of interferon beta-1b in MIRACLE clinical trial.Influenza and other respiratory viruses · 2023Trial
- Heterogeneity of treatment effect of interferon-β1b and lopinavir-ritonavir in patients with Middle East respiratory syndrome by cytokine levels.Scientific reports · 2022Trial
- Effect of a genetically engineered interferon-alpha versus traditional interferon-alpha in the treatment of moderate-to-severe COVID-19: a randomised clinical trial.Annals of medicine · 2021Trial
- Role of interferon therapy in severe COVID-19: the COVIFERON randomized controlled trial.Scientific reports · 2021Trial
- Type I IFN dynamics orchestrate protective ICAM1iScience · 2026Article
- CD4 T-cell platform for delivering interferons as an antiviral countermeasure with a focus on SARS-CoV-2.Molecular medicine (Cambridge, Mass.) · 2026Article
- Primed to overreact: virus-induced IFN contributes to antibody-mediated anaphylaxis.The Journal of clinical investigation · 2026Article
- A type I interferon-mitochondrial axis regulates efferocytosis and interferon-stimulated gene induction in macrophages.Immunity · 2026Article
- Efficacy and safety of aerosol inhalation of recombinant human interferon-α2b injection in children hospitalized with human adenovirus pneumonia: a prospective, multicenter, randomized, controlled trial in China.International journal of surgery (London, England) · 2026Article
- Next-generation single-cycle respiratory syncytial virus vaccines with increased type I interferon induction yield robust systemic and mucosal responses in mice.Frontiers in immunology · 2026Article
- Immune Delay, Beyond Immune Evasion, as a Driver of Pathogen Propagation Competence Through Neutrophil Dysregulation, to be Mitigated by Low-Frequency Electromagnetic Fields (LF-EMF).International journal of molecular sciences · 2025Review
- A Comprehensive View on the Mechanisms of Coronavirus Escaping Innate Immunity.Veterinary sciences · 2025Review
- Heterologous expression of HCoV-HKU1 ORF 7b by mouse hepatitis virus protects against severe disease during murine infection.PLoS pathogens · 2025Article
- Plasmacytoid dendritic cells are dispensable or detrimental in murine systemic or respiratory viral infections.Nature immunology · 2025Article
- Comprehensive mapping of the signaling events evoked by SARS-CoV-2 variants delta and omicron in human astrocytes.Scientific reports · 2025Article
- Balancing Host Defense and Viral Tolerance for the Development of Next-Generation Broad-Spectrum Antiviral Agents.Pathogens (Basel, Switzerland) · 2025Review
- Interferon-β treatment reverses the detrimental effect of B-cell depletion therapy on respiratory virus infection.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
305 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
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Type 1 IFNs (IFN-I) generally protect mammalian hosts from virus infections, but in some cases, IFN-I is pathogenic. Because IFN-I is protective, it is commonly used to treat virus infections for which no specific approved drug or vaccine is available. The Middle East respiratory syndrome-coronavirus (MERS-CoV) is such an infection, yet little is known about the role of IFN-I in this setting. Here, we show that IFN-I signaling is protective during MERS-CoV infection. Blocking IFN-I signaling resulted in delayed virus clearance, enhanced neutrophil infiltration, and impaired MERS-CoV-specific T cell responses. Notably, IFN-I administration within 1 day after infection (before virus titers peak) protected mice from lethal infection, despite a decrease in IFN-stimulated gene (ISG) and inflammatory cytokine gene expression. In contrast, delayed IFN-β treatment failed to effectively inhibit virus replication, increased infiltration and activation of monocytes, macrophages, and neutrophils in the lungs, and enhanced proinflammatory cytokine expression, resulting in fatal pneumonia in an otherwise sublethal infection. Together, these results suggest that the relative timing of the IFN-I response and maximal virus replication is key in determining outcomes, at least in infected mice. By extension, IFN-αβ or combination therapy may need to be used cautiously to treat viral infections in clinical settings.
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.