ArticleScience immunology2022
Administration of aerosolized SARS-CoV-2 to K18-hACE2 mice uncouples respiratory infection from fatal neuroinvasion.
Article in Science immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed.
- Triple IFN pathway deficiency sensitizes mice to human respiratory virus infection independent of human viral receptor expression.Nature communications · 2026Article
- Review
- Live attenuated vaccination protects aged chimeric ACE2 mice from severe SARS-CoV-2 pathogenicity in vivo.PLoS pathogens · 2026Article
- Platelet-derived integrin- and tetraspanin-enriched tethers exacerbate severe inflammation.Science (New York, N.Y.) · 2026Article
- SARS-CoV-2-induced damage to rat cortical neuronal networks ex vivo is mediated by the pro-inflammatory activation of the cGAS-STING pathway.Journal of neurovirology · 2025Article
- P selectin promotes SARS-CoV-2 interactions with platelets and the endothelium.The Journal of clinical investigation · 2025Article
- Review
- Comprehensive Analysis of the Impact of Weight Loss Thresholds on Mouse Models of Fatal Viral Infection.Viruses · 2025Article
- Translating animal models of SARS-CoV-2 infection to vascular, neurological and gastrointestinal manifestations of COVID-19.Disease models & mechanisms · 2025Review
- Development of a Mouse Model of Coccidioidomycosis Using an Inhalation Exposure System.Journal of fungi (Basel, Switzerland) · 2025Article
- Sustained Lung Inflammation Post-SARS-CoV-2 Infection in Mice Is Associated with Increased Pulmonary T Cells.European journal of immunology · 2025Article
- Article
- Host protein ARF1 is a proviral factor for SARS-CoV-2 and a candidate broad-spectrum therapeutic target.Nature communications · 2025Article
- Differential patterns of cross-protection against antigenically distinct variants in small animal models of SARS-CoV-2 infection.Npj viruses · 2025Article
- Ultrapotent SARS coronavirus-neutralizing single-domain antibodies that clamp the spike at its base.Nature communications · 2025Article
- Enhanced neurotropism of bovine H5N1 compared to the Vietnam H5N1 isolate in C57BL/6J mice.Npj viruses · 2025Article
- Article
- T-cell-derived IFN-γ suppresses T follicular helper cell differentiation and antibody responses.The EMBO journal · 2025Article
- Article
- T cell-derived IFN-γ Suppresses T Follicular Helper Cell Differentiation and Antibody Responses.bioRxiv : the preprint server for biology · 2025Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
22 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of a tractable small animal model faithfully reproducing human coronavirus disease 2019 pathogenesis would arguably meet a pressing need in biomedical research. Thus far, most investigators have used transgenic mice expressing the human ACE2 in epithelial cells (K18-hACE2 transgenic mice) that are intranasally instilled with a liquid severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suspension under deep anesthesia. Unfortunately, this experimental approach results in disproportionate high central nervous system infection leading to fatal encephalitis, which is rarely observed in humans and severely limits this model’s usefulness. Here, we describe the use of an inhalation tower system that allows exposure of unanesthetized mice to aerosolized virus under controlled conditions. Aerosol exposure of K18-hACE2 transgenic mice to SARS-CoV-2 resulted in robust viral replication in the respiratory tract, anosmia, and airway obstruction but did not lead to fatal viral neuroinvasion. When compared with intranasal inoculation, aerosol infection resulted in a more pronounced lung pathology including increased immune infiltration, fibrin deposition, and a transcriptional signature comparable to that observed in SARS-CoV-2–infected patients. This model may prove useful for studies of viral transmission, disease pathogenesis (including long-term consequences of SARS-CoV-2 infection), and therapeutic interventions.
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