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Updated: Mar 21, 2026

Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
Published on: November 5, 2021
SARS-CoV-2 Omicron EG.5 and JN.1 induce enhanced pathogenicity in K18-hACE2 mice compared with the early Omicron
Mandy Tsoi Man Ho1,2, Nigeer Te1, Kenrie Pui Yan Hui1,2
1School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Abstract:
The reduced pathogenicity of early SARS-CoV-2 Omicron subvariants in human ACE2-expressing K18-hACE2 mice has posed challenges for assessing vaccine and antiviral efficacy against the Omicron variant with the mouse model. Here we report the enhanced pathogenicity of the Omicron JN.1 and EG.5 lineages in K18-hACE2 mice compared with their ancestors, suggesting the potential of applying these Omicron lineages in the mouse infection model.
Insights
New Omicron subvariants, JN.1 and EG.5, show increased pathogenicity in a mouse model. This finding enhances the utility of K18-hACE2 mice for studying SARS-CoV-2 Omicron vaccine and antiviral efficacy.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Early SARS-CoV-2 Omicron subvariants exhibited reduced pathogenicity in K18-hACE2 mice.
- This limitation complicated the assessment of vaccine and antiviral efficacy using this common mouse model.
Purpose of the Study:
- To evaluate the pathogenicity of emerging SARS-CoV-2 Omicron JN.1 and EG.5 lineages in K18-hACE2 mice.
- To determine if these newer subvariants could overcome the reduced pathogenicity challenge in mouse models.
Main Methods:
- Infection of K18-hACE2 mice with SARS-CoV-2 Omicron JN.1 and EG.5 lineages.
- Comparison of pathogenicity (e.g., weight loss, viral load, clinical signs) with earlier Omicron subvariants.
Main Results:
- The Omicron JN.1 and EG.5 lineages demonstrated enhanced pathogenicity in K18-hACE2 mice compared to their predecessors.
- These findings indicate a potential for increased disease severity in the mouse model with these newer variants.
Conclusions:
- The Omicron JN.1 and EG.5 lineages exhibit increased pathogenicity in K18-hACE2 mice.
- These subvariants may be suitable for use in mouse infection models to assess SARS-CoV-2 Omicron vaccine and antiviral efficacy.
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