1921
Volume 103, Issue 3
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

Murine models of SARS-CoV-2 infection are critical for elucidating the biological pathways underlying COVID-19. Because human angiotensin-converting enzyme 2 (ACE2) is the receptor for SARS-CoV-2, mice expressing the human gene have shown promise as a potential model for COVID-19. Five mice from the transgenic mouse strain K18- were intranasally inoculated with SARS-CoV-2 Hong Kong/VM20001061/2020. Mice were followed twice daily for 5 days and scored for weight loss and clinical symptoms. Infected mice did not exhibit any signs of infection until day 4, when no other obvious clinical symptoms other than weight loss were observed. By day 5, all infected mice had lost around 10% of their original body weight but exhibited variable clinical symptoms. All infected mice showed high viral titers in the lungs as well as altered lung histology associated with proteinaceous debris in the alveolar space, interstitial inflammatory cell infiltration, and alveolar septal thickening. Overall, these results show that the K18- transgenic background can be used to establish symptomatic SARS-CoV-2 infection and can be a useful mouse model for COVID-19.

[open-access] This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Loading

Article metrics loading...

The graphs shown below represent data from March 2017
/content/journals/10.4269/ajtmh.20-0762
2020-07-28
2020-09-22
Loading full text...

Full text loading...

/deliver/fulltext/14761645/103/3/tpmd200762.html?itemId=/content/journals/10.4269/ajtmh.20-0762&mimeType=html&fmt=ahah

References

  1. Wan Y, Shang J, Graham R, Baric RS, Li F, 2020. Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus. J Virol 94: e0012720. Available at: https://doi.org/10.1128/JVI.00127-20.
    [Google Scholar]
  2. Li W et al., 2003. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426: 450454.
    [Google Scholar]
  3. Tsang KW et al., 2003. A cluster of cases of severe acute respiratory syndrome in Hong Kong. N Engl J Med 348: 19771985.
    [Google Scholar]
  4. Shang J, Ye G, Shi K, Wan Y, Luo C, Aihara H, Geng Q, Auerbach A, Li F, 2020. Structural basis of receptor recognition by SARS-CoV-2. Nature 581: 221224.
    [Google Scholar]
  5. McCray PB et al., 2007. Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus. J Virol 81: 813821.
    [Google Scholar]
  6. Bao L et al., 2020. The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice. Nature (Epub ahead of print). Available at: https://doi.org/10.1038/s41586-020-2312-y.
    [Google Scholar]
  7. Sun SH et al., 2020. A mouse model of SARS-CoV-2 infection and pathogenesis. Cell Host Microbe 28: 124133.e4.
    [Google Scholar]
  8. Menachery VD et al., 2016. SARS-like WIV1-CoV poised for human emergence. Proc Natl Acad Sci USA 113: 30483053.
    [Google Scholar]
  9. Jiang R-D et al., 2020. Pathogenesis of SARS-CoV-2 in transgenic mice expressing human angiotensin-converting enzyme 2. Cell 182: 50–58.e8. Available at: https://doi.org/10.1016/j.cell.2020.05.027.
  10. Hassan AO et al., 2020. A SARS-CoV-2 infection model in mice demonstrates protection by neutralizing antibodies. Cell S0092-8674(20)30742-X. Available at: https://doi.org/10.1016/j.cell.2020.06.011.
    [Google Scholar]
  11. Matute-Bello G, Downey G, Moore BB, Groshong SD, Matthay MA, Slutsky AS, Kuebler WM, Acute Lung Injury in Animals Study Group, 2011. An official American Thoracic Society workshop report: features and measurements of experimental acute lung injury in animals. Am J Respir Cell Mol Biol 44: 725738.
    [Google Scholar]
  12. Zhang L, Yang J-R, Zhang Z, Lin Z, 2020. Genomic variations of SARS-CoV-2 suggest multiple outbreak sources of transmission. medRxiv 2020.02.25.20027953. Available at: https://doi.org/10.1101/2020.02.25.20027953.
    [Google Scholar]
  13. Baer A, Kehn-Hall K, 2014. Viral concentration determination through plaque assays: using traditional and novel overlay systems. J Vis Exp 93: e52065. Available at: https://doi.org/10.3791/52065.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.20-0762
Loading
/content/journals/10.4269/ajtmh.20-0762
Loading

Data & Media loading...

  • Received : 29 Jun 2020
  • Accepted : 23 Jul 2020
  • Published online : 28 Jul 2020
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error