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SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract.

Publication ,  Journal Article
Hou, YJ; Okuda, K; Edwards, CE; Martinez, DR; Asakura, T; Dinnon, KH; Kato, T; Lee, RE; Yount, BL; Mascenik, TM; Chen, G; Olivier, KN; Sun, L ...
Published in: Cell
July 23, 2020

The mode of acquisition and causes for the variable clinical spectrum of coronavirus disease 2019 (COVID-19) remain unknown. We utilized a reverse genetics system to generate a GFP reporter virus to explore severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis and a luciferase reporter virus to demonstrate sera collected from SARS and COVID-19 patients exhibited limited cross-CoV neutralization. High-sensitivity RNA in situ mapping revealed the highest angiotensin-converting enzyme 2 (ACE2) expression in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) versus distal (low) pulmonary epithelial cultures. COVID-19 autopsied lung studies identified focal disease and, congruent with culture data, SARS-CoV-2-infected ciliated and type 2 pneumocyte cells in airway and alveolar regions, respectively. These findings highlight the nasal susceptibility to SARS-CoV-2 with likely subsequent aspiration-mediated virus seeding to the lung in SARS-CoV-2 pathogenesis. These reagents provide a foundation for investigations into virus-host interactions in protective immunity, host susceptibility, and virus pathogenesis.

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Published In

Cell

DOI

EISSN

1097-4172

Publication Date

July 23, 2020

Volume

182

Issue

2

Start / End Page

429 / 446.e14

Location

United States

Related Subject Headings

  • Virus Replication
  • Virulence
  • Vero Cells
  • Serine Endopeptidases
  • SARS-CoV-2
  • Reverse Genetics
  • Respiratory System
  • Pneumonia, Viral
  • Peptidyl-Dipeptidase A
  • Pandemics
 

Citation

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Hou, Y. J., Okuda, K., Edwards, C. E., Martinez, D. R., Asakura, T., Dinnon, K. H., … Baric, R. S. (2020). SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract. Cell, 182(2), 429-446.e14. https://doi.org/10.1016/j.cell.2020.05.042
Hou, Yixuan J., Kenichi Okuda, Caitlin E. Edwards, David R. Martinez, Takanori Asakura, Kenneth H. Dinnon, Takafumi Kato, et al. “SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract.Cell 182, no. 2 (July 23, 2020): 429-446.e14. https://doi.org/10.1016/j.cell.2020.05.042.
Hou YJ, Okuda K, Edwards CE, Martinez DR, Asakura T, Dinnon KH, et al. SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract. Cell. 2020 Jul 23;182(2):429-446.e14.
Hou, Yixuan J., et al. “SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract.Cell, vol. 182, no. 2, July 2020, pp. 429-446.e14. Pubmed, doi:10.1016/j.cell.2020.05.042.
Hou YJ, Okuda K, Edwards CE, Martinez DR, Asakura T, Dinnon KH, Kato T, Lee RE, Yount BL, Mascenik TM, Chen G, Olivier KN, Ghio A, Tse LV, Leist SR, Gralinski LE, Schäfer A, Dang H, Gilmore R, Nakano S, Sun L, Fulcher ML, Livraghi-Butrico A, Nicely NI, Cameron M, Cameron C, Kelvin DJ, de Silva A, Margolis DM, Markmann A, Bartelt L, Zumwalt R, Martinez FJ, Salvatore SP, Borczuk A, Tata PR, Sontake V, Kimple A, Jaspers I, O’Neal WK, Randell SH, Boucher RC, Baric RS. SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract. Cell. 2020 Jul 23;182(2):429-446.e14.
Journal cover image

Published In

Cell

DOI

EISSN

1097-4172

Publication Date

July 23, 2020

Volume

182

Issue

2

Start / End Page

429 / 446.e14

Location

United States

Related Subject Headings

  • Virus Replication
  • Virulence
  • Vero Cells
  • Serine Endopeptidases
  • SARS-CoV-2
  • Reverse Genetics
  • Respiratory System
  • Pneumonia, Viral
  • Peptidyl-Dipeptidase A
  • Pandemics