Neuroinvasion and Neurotropism by SARS-CoV-2 Variants in the K18-hACE2 Mouse
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture and Viruses
2.2. Biosafety
2.3. Animals and Virus Infections
2.4. Tissue Collection, Preparation and Processing
2.5. Histology, Immunohistology
2.6. RNA In Situ Hybridization (RNA-ISH)
3. Results
3.1. In K18-hACE2 Mice, SARS-CoV-2 Pango B, Alpha, Beta and Delta Variant Infection Is Frequently Accompanied by Virus Spread into the Central Nervous System
3.2. In K18-hACE2 Mice, SARS-CoV-2 Infection in the Central Nervous System Is Restricted to Neurons and Spreads in the Brain and into the Spinal Cord
3.3. SARS-CoV-2 Infection of the Brain Is Associated with Diffuse Microglial Activation and a Mild Macrophage and T Cell Dominated Inflammatory Response
3.4. There Is No Evidence of Viral Infection of Glial Cells, Endothelial Cells or Leukocytes or of Neuronal Cell Death, Axonal Damage or Demyelination in Association with SARS-CoV-2 Infection, but of Apoptotic Death of Endothelial Cells and Immune Cells
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Virus 1 | Virus 2 | ||||
---|---|---|---|---|---|
Cohort | Virus | PFU | Virus | PFU | DPI (pos) |
1 | Pango B | 104 | - | - | 3 (0/4), 7 (7/9) |
2 | IAV X31 | 102 | Pango B | 104 | 3 (0/4), 7 (3/4) |
3 | Pango B | 103 | - | - | 6 (6/6) |
4 | Alpha | 103 | - | - | 3 (0/4), 6 (2/2) |
5 | Beta | 103 | - | - | 3 (2/4), 6 (2/2) |
6 | Delta | 103 | - | - | 3 (0/4), 5 (6/8), 6 (3/6), 7 (5/6) |
7 | Omicron BA.1 | 103 | - | - | 5 (0/5), 6 (0/6), 7 (0/6) |
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Seehusen, F.; Clark, J.J.; Sharma, P.; Bentley, E.G.; Kirby, A.; Subramaniam, K.; Wunderlin-Giuliani, S.; Hughes, G.L.; Patterson, E.I.; Michael, B.D.; et al. Neuroinvasion and Neurotropism by SARS-CoV-2 Variants in the K18-hACE2 Mouse. Viruses 2022, 14, 1020. https://doi.org/10.3390/v14051020
Seehusen F, Clark JJ, Sharma P, Bentley EG, Kirby A, Subramaniam K, Wunderlin-Giuliani S, Hughes GL, Patterson EI, Michael BD, et al. Neuroinvasion and Neurotropism by SARS-CoV-2 Variants in the K18-hACE2 Mouse. Viruses. 2022; 14(5):1020. https://doi.org/10.3390/v14051020
Chicago/Turabian StyleSeehusen, Frauke, Jordan J. Clark, Parul Sharma, Eleanor G. Bentley, Adam Kirby, Krishanthi Subramaniam, Sabina Wunderlin-Giuliani, Grant L. Hughes, Edward I. Patterson, Benedict D. Michael, and et al. 2022. "Neuroinvasion and Neurotropism by SARS-CoV-2 Variants in the K18-hACE2 Mouse" Viruses 14, no. 5: 1020. https://doi.org/10.3390/v14051020