SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract
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Hou, Yixuan J, et al. Sars-cov-2 Reverse Genetics Reveals a Variable Infection Gradient In the Respiratory Tract. 2020. https://doi.org/10.17615/1qs8-pe15APA
Hou, Y., Okuda, K., Edwards, C., Martinez, D., Asakura, T., Dinnon Iii, K., Kato, T., Lee, R., Yount, B., Mascenik, T., Chen, G., Olivier, K., Ghio, A., Tse, L., Leist, S., Gralinski, L., Schäfer, A., Dang, H., Gilmore, R., Nakano, S., Sun, L., Fulcher, M., Livraghi Butrico, A., Nicely, N., Cameron, M., Cameron, C., Kelvin, D., De Silva, A., Margolis, D., Markmann, A., Bartelt, L., Zumwalt, R., Martinez, F., Salvatore, S., Borczuk, A., Tata, P., Sontake, V., Kimple, A., Jaspers, I., O'neal, W., Randell, S., Boucher, R., & Baric, R. (2020). SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract. https://doi.org/10.17615/1qs8-pe15Chicago
Hou, Yixuan J., Kenichi Okuda, Caitlin E Edwards, David R Martinez, Takanori Asakura, Kenneth H Dinnon Iii, Takafumi Kato et al. 2020. Sars-Cov-2 Reverse Genetics Reveals a Variable Infection Gradient In the Respiratory Tract. https://doi.org/10.17615/1qs8-pe15- Creator
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Hou, Yixuan J.
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology
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Okuda, Kenichi
- Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
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Edwards, Caitlin E.
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology
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Martinez, David R.
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology
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Asakura, Takanori
- Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
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Dinnon III, Kenneth H.
- Affiliation: School of Medicine, Department of Microbiology and Immunology
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Kato, Takafumi
- Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
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Lee, Rhianna E.
- Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
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Yount, Boyd L.
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology
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Mascenik, Teresa M.
- Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
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Chen, Gang
- Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
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Olivier, Kenneth N.
- Other Affiliation: National Institutes of Health
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Ghio, Andrew
- Other Affiliation: Environmental Protection Agency
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Tse, Longping V.
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology
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Leist, Sarah R.
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology
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Gralinski, Lisa E.
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology
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Schäfer, Alexandra
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology
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Dang, Hong
- Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
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Gilmore, Rodney
- Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
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Nakano, Satoko
- Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
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Sun, Ling
- Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
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Fulcher, M. Leslie
- Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
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Livraghi-Butrico, Alessandra
- Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
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Nicely, Nathan I.
- Affiliation: School of Medicine
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Cameron, Mark
- Other Affiliation: Case Western Reserve University
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Cameron, Cheryl
- Other Affiliation: Case Western Reserve University
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Kelvin, David J.
- Other Affiliation: Dalhousie University
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de Silva, Aravinda
- Affiliation: School of Medicine, Department of Microbiology and Immunology
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Margolis, David M.
- Affiliation: School of Medicine, Department of Microbiology and Immunology
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Markmann, Alena
- Affiliation: School of Medicine, Department of Medicine
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Bartelt, Luther
- Affiliation: School of Medicine, Department of Medicine
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Zumwalt, Ross
- Other Affiliation: University of New Mexico
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Martinez, Fernando J.
- Other Affiliation: Cornell University
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Salvatore, Steven P.
- Other Affiliation: Cornell University
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Borczuk, Alain
- Other Affiliation: Cornell University
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Tata, Purushothama R.
- Other Affiliation: Duke University Medical Center
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Sontake, Vishwaraj
- Other Affiliation: Duke University Medical Center
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Kimple, Adam
- Affiliation: School of Medicine, Department of Otolaryngology/Head and Neck Surgery
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Jaspers, Ilona
- Affiliation: School of Medicine, Department of Pediatrics
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O'Neal, Wanda K.
- Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
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Randell, Scott H.
- Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
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Boucher, Richard C.
- Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
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Baric, Ralph S.
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology
- Abstract
- 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) expres-sion 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-in-fected ciliated and type 2 pneumocyte cells in airway and alveolar regions, respectively. These findings high-light 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 in-teractions in protective immunity, host susceptibility, and virus pathogenesis.
- Date of publication
- 2020
- Keyword
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- Resource type
- Article
- Rights statement
- In Copyright
- Journal title
- Cell
- Language
- English
- Version
- Postprint
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