ArticleJournal of virology2022
SARS-CoV-2 Causes Lung Infection without Severe Disease in Human ACE2 Knock-In Mice.
Article in Journal of virology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 2 of them syntheses that pooled it.
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Who cites it
61 citing papers in PubMed, 2 syntheses or guidelines pooled it, 85 citations in OpenAlex.
- Neurological Manifestations of SARS-CoV-2.Viruses · 2025Pooled it
- The Reassessed Potential of SARS-CoV-2 Attenuation for COVID-19 Vaccine Development-A Systematic Review.Viruses · 2022Pooled it
- Triple IFN pathway deficiency sensitizes mice to human respiratory virus infection independent of human viral receptor expression.Nature communications · 2026Article
- Article
- Effects of Exogenous SARS-CoV-2 S1 Protein and mRNA Vaccines on Mixed Neuronal-Glial Cell Cultures.Medicina (Kaunas, Lithuania) · 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
- Impact of FcRn antagonism on vaccine-induced protective immune responses against viral challenge in COVID-19 and influenza mouse vaccination models.Human vaccines & immunotherapeutics · 2025Article
- Exploring the biological mechanisms of severe COVID-19 in the elderly: Insights from an aged mouse model.Virulence · 2025Article
- Current Advances and Applications of Animal Models in SARS-CoV-2 Pathogenesis and Vaccine Development.Microorganisms · 2025Review
- Article
- Sequential SARS-CoV-2 mRNA Vaccination Induces Anti-Idiotype (Anti-ACE2) Antibodies in K18 Human ACE2 Transgenic Mice.Vaccines · 2025Article
- A trivalent mucosal vaccine encoding phylogenetically inferred ancestral RBD sequences confers pan-Sarbecovirus protection in mice.Cell host & microbe · 2024Article
- Staggered immunization with mRNA vaccines encoding SARS-CoV-2 polymerase or spike antigens broadens the T cell epitope repertoire.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Influence of Th1 versus Th2 immune bias on viral, pathological, and immunological dynamics in SARS-CoV-2 variant-infected human ACE2 knock-in mice.EBioMedicine · 2024Article
- Infiltrating monocytes drive cardiac dysfunction in a cardiomyocyte-restricted mouse model of SARS-CoV-2 infection.Journal of virology · 2024Article
- Human ACE2 Gene Replacement Mice Support SARS-CoV-2 Viral Replication and Nonlethal Disease Progression.ImmunoHorizons · 2024Article
- S309-CAR-NK cells bind the Omicron variantsJournal of virology · 2024Article
- Article
- The SARS-CoV-2 Spike is a virulence determinant and plays a major role on the attenuated phenotype of Omicron virus in a feline model of infection.Journal of virology · 2024Article
- Adaptation of SARS-CoV-2 to ACE2Journal of virology · 2024Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The development of mouse models for coronavirus disease 2019 (COVID-19) has enabled testing of vaccines and therapeutics and defining aspects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis. SARS-CoV-2 disease is severe in K18 transgenic mice (K18-hACE2 Tg) expressing human angiotensin-converting enzyme 2 (hACE2), the SARS-CoV-2 receptor, under an ectopic cytokeratin promoter, with high levels of infection measured in the lung and brain. Here, we evaluated SARS-CoV-2 infection in hACE2 knock-in (KI) mice that express hACE2 under an endogenous promoter in place of murine ACE2 (mACE2). Intranasal inoculation of hACE2 KI mice with SARS-CoV-2 WA1/2020 resulted in substantial viral replication within the upper and lower respiratory tracts with limited spread to extrapulmonary organs. However, SARS-CoV-2-infected hACE2 KI mice did not lose weight and developed limited pathology. Moreover, no significant differences in viral burden were observed in hACE2 KI mice infected with B.1.1.7 or B.1.351 variants compared to the WA1/2020 strain. Because the entry mechanisms of SARS-CoV-2 in mice remain uncertain, we evaluated the impact of the naturally occurring, mouse-adapting N501Y mutation by comparing infection of hACE2 KI, K18-hACE2 Tg, ACE2-deficient, and wild-type C57BL/6 mice. The N501Y mutation minimally affected SARS-CoV-2 infection in hACE2 KI mice but was required for viral replication in wild-type C57BL/6 mice in a mACE2-dependent manner and augmented pathogenesis in the K18-hACE2 Tg mice. Thus, the N501Y mutation likely enhances interactions with mACE2 or hACE2
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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 OpenQuestion graph.