ArticleProceedings of the National Academy of Sciences of the United States of America2023
SARS-CoV-2 mouse adaptation selects virulence mutations that cause TNF-driven age-dependent severe disease with human correlates.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Efferocytosis of apoptotic bodies drives SARS-CoV-2 infection and macrophage inflammation.Nature communications · 2026Article
- Respiratory Organ-on-a-Chip for Disease Modeling: From Architecture to Functional Integration.Advanced healthcare materials · 2026Review
- IFITM3 deficiency drives SARS-CoV-2 adaptation while preserving variant-specific traits.Nature communications · 2026Article
- Non-apoptotic caspase-8 is critical for orchestrating exaggerated inflammation during severe SARS-CoV-2 infection.Nature communications · 2025Article
- Paternal SARS-CoV-2 infection impacts sperm small noncoding RNAs and increases anxiety in offspring in a sex-dependent manner.Nature communications · 2025Article
- Pyroptosis in Respiratory Virus Infections: A Narrative Review of Mechanisms, Pathophysiology, and Potential Therapeutic Interventions.Microorganisms · 2025Review
- Current Advances and Applications of Animal Models in SARS-CoV-2 Pathogenesis and Vaccine Development.Microorganisms · 2025Review
- IL-1β drives SARS-CoV-2-induced disease independently of the inflammasome and pyroptosis signalling.Cell death and differentiation · 2025Article
- Investigating the impact of severe maternal SARS-CoV-2 infection on infant DNA methylation and neurodevelopment.Molecular psychiatry · 2025Article
- A novel PLpro inhibitor improves outcomes in a pre-clinical model of long COVID.Nature communications · 2025Article
- Targeted labeling and depletion of alveolar macrophages using VeDTR mouse technology.iScience · 2025Article
- Tuning the tropism and infectivity of SARS-CoV-2 virus-like particles for mRNA delivery.Nucleic acids research · 2025Article
- ACE2, From the Kidney to SARS-CoV-2: Donald Seldin Award Lecture 2023.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Article
- TNF-α exacerbates SARS-CoV-2 infection by stimulating CXCL1 production from macrophages.PLoS pathogens · 2024Article
- Review
- CD4Science advances · 2024Article
- Immunobiology of COVID-19: Mechanistic and therapeutic insights from animal models.Zoological research · 2024Review
- Identification of FasL as a crucial host factor driving COVID-19 pathology and lethality.Cell death and differentiation · 2024Article
- Fourth dose of microneedle array patch of SARS-CoV-2 S1 protein subunit vaccine elicits robust long-lasting humoral responses in mice.International immunopharmacology · 2024Article
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Authors and funding
24 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The diversity of COVID-19 disease in otherwise healthy people, from seemingly asymptomatic infection to severe life-threatening disease, is not clearly understood. We passaged a naturally occurring near-ancestral SARS-CoV-2 variant, capable of infecting wild-type mice, and identified viral genomic mutations coinciding with the acquisition of severe disease in young adult mice and lethality in aged animals. Transcriptomic analysis of lung tissues from mice with severe disease elucidated a host antiviral response dominated mainly by interferon and IL-6 pathway activation in young mice, while in aged animals, a fatal outcome was dominated by TNF and TGF-β signaling. Congruent with our pathway analysis, we showed that young TNF-deficient mice had mild disease compared to controls and aged TNF-deficient animals were more likely to survive infection. Emerging clinical correlates of disease are consistent with our preclinical studies, and our model may provide value in defining aberrant host responses that are causative of severe COVID-19.
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