SARS-CoV-2 Variant-Specific Infectivity and Immune Profiles Are Detectable in a Humanized Lung Mouse Model
Abstract
:1. Introduction
2. Materials and Methods
2.1. Ethics Statement
2.2. Humanized TKO-BLT-L Mice
2.3. Analysis of Human Immune Cell Reconstitution
2.4. Ultrasound
2.5. Immunohistochemical Analysis
2.6. Viruses
2.7. Viral Challenge
2.8. Quantification of Infection
2.9. Human Cytokine and Chemokine Profile
2.10. Statistical Analysis
3. Results
3.1. Subcutaneously Implanted Human Lung Tissue Expands into Highly Vascularized Lung Organoids
3.2. Systemic Human Immune Cell Reconstitution Is not Altered by Implantation of Lung Organoids
3.3. Lung Organoids Develop Structures and Contain Cell Types and SARS-CoV-2 Entry Molecules Similar to Human Lungs
3.4. Implanted Lung Tissues in TKO-BLT-L Mice Become Reconstituted with Human Immune Cells
3.5. Differences in the Viral Infectivity and Persistence of SARS-CoV-2 Variants Were Detectable in TKO-BLT-L Mice
3.6. The Immune Responses to SARS-CoV-2 Infection Differed between Viral Variants and Required the Systemic Human Immune System of TKO-BLT-L Mice to Mediate Viral Clearance
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Per mL blood | % of Live | % of CD45+ | % of T Cells | % of CD45+ | % of DC | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
2 CD45 | CD45 | T Cells | CD4 | CD8 | CD14 | CD33 | B Cells | NK cells | DC | mDC | pDC | |
BLT-L 12 1wps | 3 4.69 × 105 (±5.23 × 104) | 61.37 (±11.81) | 70.84 (±13.91) | 73.95 (±4.33) | 23.51 (±3.77) | 0.76 (±0.40) | 4.54 (±2.94) | 26.33 (±19.32) | 0.27 (±0.24) | 3.69 (±2.16) | 0.28 (±0.09) | 0.29 (±0.18) |
BLT 12 wps | 4.59 × 105 (±3.08 × 105 | 58.75 (±14.49) | 74.84 (±17.21) | 71.13 (±8.72) | 16.54 (±12.40) | 1.16 (±1.21) | 2.93 (±2.38) | 19.37 (±15.07) | 0.49 (±0.73) | 3.27 (±2.32) | 0.25 (±0.27) | 0.08 (±0.11) |
p-Value | 0.5720 | 0.7930 | 0.8971 | 0.1331 | 0.5844 | 0.4738 | 0.5326 | 0.7496 | 0.3589 | 0.7462 | 0.5999 | 0.1248 |
% of Live | % of CD45+ | % of T Cells | % of CD45+ | % of DC | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|
CD45 | T Cells | CD4 | CD8 | CD14 | CD33 | B Cells | NK | DC | mDC | pDC | |
1 Lung organoid | 3 26.31 (±15.42) | 64.69 (±13.53) | 0.14 (±0.11) | 31.50 (±6.38) | 2.82 (±2.91) | 8.53 (±4.96) | 20.80 (±8.37) | 0.54 (±0.39) | 3.38 (±1.48) | 21.83 (±6.94) | 0.29 (±0.38) |
2 Adult lung | 11 | 48 | 0.46 | 25 | 17.1 | 41.3 | 3.03 | 3.04 | 13.3 | 2.37 | 0.87 |
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Di, Y.; Lew, J.; Goncin, U.; Radomska, A.; Rout, S.S.; Gray, B.E.T.; Machtaler, S.; Falzarano, D.; Lavender, K.J. SARS-CoV-2 Variant-Specific Infectivity and Immune Profiles Are Detectable in a Humanized Lung Mouse Model. Viruses 2022, 14, 2272. https://doi.org/10.3390/v14102272
Di Y, Lew J, Goncin U, Radomska A, Rout SS, Gray BET, Machtaler S, Falzarano D, Lavender KJ. SARS-CoV-2 Variant-Specific Infectivity and Immune Profiles Are Detectable in a Humanized Lung Mouse Model. Viruses. 2022; 14(10):2272. https://doi.org/10.3390/v14102272
Chicago/Turabian StyleDi, Yunyun, Jocelyne Lew, Una Goncin, Anna Radomska, Saurav S. Rout, Bridget E. T. Gray, Steven Machtaler, Darryl Falzarano, and Kerry J. Lavender. 2022. "SARS-CoV-2 Variant-Specific Infectivity and Immune Profiles Are Detectable in a Humanized Lung Mouse Model" Viruses 14, no. 10: 2272. https://doi.org/10.3390/v14102272
APA StyleDi, Y., Lew, J., Goncin, U., Radomska, A., Rout, S. S., Gray, B. E. T., Machtaler, S., Falzarano, D., & Lavender, K. J. (2022). SARS-CoV-2 Variant-Specific Infectivity and Immune Profiles Are Detectable in a Humanized Lung Mouse Model. Viruses, 14(10), 2272. https://doi.org/10.3390/v14102272