ArticleCritical care explorations2025
Interferon Regulatory Factor 3 Exacerbates the Severity of COVID-19 in Mice.
Article in Critical care explorations, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Loss of 7-Dehydrocholesterol Reductase mediated cholesterol biosynthesis activates IRF3 and inhibits control ofbioRxiv : the preprint server for biology · 2026Article
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Authors and funding
7 authors.
Funding
Abstract
contextSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019, causing the COVID-19 pandemic. While most infected people experienced mild illness, others progressed to severe disease, characterized by hyperinflammation and respiratory distress. There is still much to learn about the innate immune response to this virus. Interferon regulatory factor 3 (IRF3) is a transcription factor that is activated when pattern recognition receptors detect viruses. Upon activation, IRF3 induces the expression of interferon beta (IFN-β) and interferon-stimulated genes, which protect the host from viral infection. However, coronaviruses antagonize this pathway, delaying type 1 IFN production. It is, therefore, unclear how IRF3 influences COVID-19 disease. Our prior reports showed that IRF3 promotes harmful inflammation during bacterial sepsis in mice. HYPOTHESIS: We hypothesized that IRF3 cannot effectively control the SARS-CoV-2 viral load and instead promotes harmful inflammation during severe COVID-19. METHODS AND MODELS: We used mice transgenic for the human angiotensin converting-enzyme 2 transgene, driven by the keratin 18 promoter (K18-ACE2 mice) that were IRF3 deficient or IRF3 sufficient to test how IRF3 influences COVID-19 disease.
resultsUpon infection with SARS-CoV-2, K18-ACE2 mice showed a dose-dependent disease, characterized by mortality, lethargy, weight loss, and lung pathology, reminiscent of clinical COVID-19. However, K18-ACE2 mice lacking IRF3 were protected from severe disease with reduced mortality (84.6% vs. 100%) and disease score. We found that IRF3 promoted IFN-β production in the lungs and reprogrammed the cytokine profile, while viral load in the lungs was similar in the presence or absence of IRF3. INTERPRETATIONS AND
conclusionsThese data indicated that IRF3 played a detrimental role in murine COVID-19 associated with changes in IFN-β and inflammatory cytokines.
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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 Socratic graph.