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Updated: Aug 18, 2025
Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
Published on: November 5, 2021
Comparison of the Pathogenicity of SARS-CoV-2 Delta and Omicron Variants by Analyzing the Expression Patterns of
Kuruppu Arachchillage Praboda Priyangi Kuruppuarachchi1,2, Yunyueng Jang1,2, Sang Heui Seo1,2
1Laboratory of Influenza Research, College of Veterinary Medicine, Chungnam National University, 34134 Daejeon, Republic of Korea.
Background:
The recently emerged variants of the severe acute respiratory coronavirus 2 (SARS-CoV-2) pose a threat to public health. Understanding the pathogenicity of these variants is a salient factor in the development of effective SARS-CoV-2 therapeutics. This study aimed to compare the expression patterns of genes involved in immune responses in K18-hACE2 mice infected with the wild-type, Delta, and Omicron SARS-CoV-2 variants.
Methods:
K18-hACE2 mice were intranasally infected with either wild-type (B.1), Delta (B.1.617.2), or Omicron (B.1.1.529) variants. On day 6 post-infection, lung, brain, and kidney tissues were collected from each variant-infected group. The mRNA expression levels of 39 immune response genes in all three groups were compared by RT-qPCR. Viral titers were measured using the median tissue culture infectious dose (TCID50) assay and expressed as Log10 TCID50/0.1 g. The statistical significance of the differences in gene expression was determined by one-way analysis of variance (ANOVA) (alpha = 0.05).
Results:
The expression of toll-like receptors (TLRs) was upregulated in the lung and brain tissues of the wild-type- and Delta-infected groups but not in those of the Omicron-infected group. The highest expression of cytokines, including interleukin (IL)-1α, IL-1β, IL-17α, interferon, and tumor necrosis factors, was observed in the lungs of mice infected with the wild-type variant. Additionally, CCL4, CCL11, CXCL9, and CXCL10 were upregulated (>3-fold) in wild-type-infected mice, with markedly higher expressions in the brain than in the lungs. Most of the apoptotic factors were mainly expressed in the brain tissues of Omicron-infected mice (caspase 8, caspase 9, p53, Bax, Bak, BCL-2, and Bcl-XL), whereas neither the lung nor kidney showed more than 3-fold upregulation of these apoptotic factors.
Conclusions:
Collectively, our findings revealed that the wild-type SARS-CoV-2 variant exhibited the highest pathogenicity, followed by the Delta variant, then the Omicron variant.
Insights
The wild-type SARS-CoV-2 variant showed the highest pathogenicity, followed by Delta, then Omicron. This comparative study analyzed immune gene expression in K18-hACE2 mice to understand variant virulence.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Emerging SARS-CoV-2 variants pose significant public health risks.
- Understanding variant pathogenicity is crucial for developing effective therapeutics.
- This study investigates immune gene expression differences across SARS-CoV-2 variants.
Purpose of the Study:
- To compare the pathogenicity of wild-type, Delta, and Omicron SARS-CoV-2 variants.
- To analyze immune response gene expression patterns in K18-hACE2 mice infected with different SARS-CoV-2 variants.
- To identify key immune markers associated with variant-specific pathogenicity.
Main Methods:
- K18-hACE2 mice were infected with wild-type, Delta, or Omicron SARS-CoV-2 variants.
- Lung, brain, and kidney tissues were collected on day 6 post-infection.
- RT-qPCR was used to compare mRNA expression of 39 immune genes; viral titers were measured via TCID50 assay.
Main Results:
- Toll-like receptor (TLR) expression was upregulated in wild-type and Delta groups, but not Omicron.
- Wild-type infection led to the highest expression of cytokines (e.g., IL-1α, IL-1β) and chemokines (e.g., CCL4, CXCL9) in lungs.
- Omicron infection primarily upregulated apoptotic factors in brain tissue, unlike wild-type and Delta variants.
Conclusions:
- Wild-type SARS-CoV-2 exhibited the highest pathogenicity.
- The Delta variant demonstrated intermediate pathogenicity.
- The Omicron variant displayed the lowest pathogenicity among the tested variants.
