Spatiotemporal Characterization of Changes in the Respiratory Tract and the Nervous System, Including the Eyes in SARS-CoV-2-Infected K18-hACE2 Mice
Abstract
1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Study Design
2.3. Histopathology
2.4. Immunohistochemistry
2.5. Evaluation of Results
2.6. Digital Analysis of Immunohistochemical Results
2.7. Real-Time RT-qPCR
2.8. Statistical Analysis
3. Results
3.1. Nasal Tissue
3.1.1. Histology of Nasal Tissue
Histology of Olfactory Epithelium
Histology of Respiratory Epithelium
3.1.2. Immunohistochemistry of Nasal Tissue
SARS-CoV-2-NP Immunohistochemistry of Olfactory Epithelium
SARS-CoV-2-NP Immunohistochemistry of Respiratory Epithelium
3.2. Lung Tissue
3.2.1. Histology of Lung Tissue
3.2.2. SARS-CoV-2-NP Immunohistochemistry of Lung Tissue
3.2.3. RT-qPCR of Lung Tissue
3.3. Brain Tissue
3.3.1. Histology of Brain Tissue
3.3.2. Immunohistochemistry of Brain Tissue
SARS-CoV-2-NP Immunohistochemistry
Iba-1 Immunohistochemistry
CD3 Immunohistochemistry
CD45R and Myeloperoxidase Immunohistochemistry
Beta-Amyloid Precursor Protein, Kinesin, and Neurofilament Immunohistochemistry
3.3.3. RT-qPCR of Brain Tissue
3.4. Globes and Optic Chiasms
3.4.1. Histology of Globes and Optic Chiasms
3.4.2. Immunohistochemistry of Globes
SARS-CoV-2-NP Immunohistochemistry
Iba-1, CD3, Glial Fibrillary Acidic Protein (GFAP) and Glutamine Synthetase (GS), β-Tubulin, Neurofilaments, and Caspase 3 Immunohistochemistry
4. Discussion
4.1. Olfactory Epithelium Shows Prolonged SARS-CoV-2 Infection Compared to Respiratory Epithelium in K18-hACE2 Mice
4.2. Aveolar-Restricted SARS-CoV-2 Pneumonia in K18-hACE2 Mice
4.3. Mononuclear Meningoencephalitis and Microgliosis Represent Common Features of SARS-CoV-2 Infection
4.4. Neurofilament Accumulation Points to Axonal Transport Dysfunction in the CNS
4.5. SARS-CoV-2 Invades Ocular Tissues via Neuronal Routes in K18-hACE2 Mice
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Rosiak, M.; Schreiner, T.; Beythien, G.; Leitzen, E.; Ulianytska, A.; Allnoch, L.; Becker, K.; Michaely, L.M.; Lockow, S.; Clever, S.; et al. Spatiotemporal Characterization of Changes in the Respiratory Tract and the Nervous System, Including the Eyes in SARS-CoV-2-Infected K18-hACE2 Mice. Viruses 2025, 17, 963. https://doi.org/10.3390/v17070963
Rosiak M, Schreiner T, Beythien G, Leitzen E, Ulianytska A, Allnoch L, Becker K, Michaely LM, Lockow S, Clever S, et al. Spatiotemporal Characterization of Changes in the Respiratory Tract and the Nervous System, Including the Eyes in SARS-CoV-2-Infected K18-hACE2 Mice. Viruses. 2025; 17(7):963. https://doi.org/10.3390/v17070963
Chicago/Turabian StyleRosiak, Malgorzata, Tom Schreiner, Georg Beythien, Eva Leitzen, Anastasiya Ulianytska, Lisa Allnoch, Kathrin Becker, Lukas M. Michaely, Sandra Lockow, Sabrina Clever, and et al. 2025. "Spatiotemporal Characterization of Changes in the Respiratory Tract and the Nervous System, Including the Eyes in SARS-CoV-2-Infected K18-hACE2 Mice" Viruses 17, no. 7: 963. https://doi.org/10.3390/v17070963
APA StyleRosiak, M., Schreiner, T., Beythien, G., Leitzen, E., Ulianytska, A., Allnoch, L., Becker, K., Michaely, L. M., Lockow, S., Clever, S., Meyer zu Natrup, C., Volz, A., Baumgärtner, W., Ciurkiewicz, M., Hülskötter, K., & Gregor, K. M. (2025). Spatiotemporal Characterization of Changes in the Respiratory Tract and the Nervous System, Including the Eyes in SARS-CoV-2-Infected K18-hACE2 Mice. Viruses, 17(7), 963. https://doi.org/10.3390/v17070963