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SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract.
- Source :
-
Cell [Cell] 2020 Jul 23; Vol. 182 (2), pp. 429-446.e14. Date of Electronic Publication: 2020 May 27. - Publication Year :
- 2020
-
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) 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.<br />Competing Interests: Declaration of Interests The authors declare no competing financial interests.<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Subjects :
- Aged
Angiotensin-Converting Enzyme 2
Animals
Antibodies, Monoclonal immunology
Antibodies, Neutralizing immunology
Betacoronavirus immunology
Betacoronavirus pathogenicity
COVID-19
Cell Line
Cells, Cultured
Chlorocebus aethiops
Coronavirus Infections immunology
Coronavirus Infections therapy
Cystic Fibrosis pathology
DNA, Recombinant
Female
Furin metabolism
Humans
Immunization, Passive
Lung metabolism
Lung pathology
Lung virology
Male
Middle Aged
Nasal Mucosa metabolism
Nasal Mucosa pathology
Nasal Mucosa virology
Pandemics
Peptidyl-Dipeptidase A metabolism
Pneumonia, Viral immunology
Respiratory System pathology
SARS-CoV-2
Serine Endopeptidases metabolism
Vero Cells
Virulence
Virus Replication
COVID-19 Serotherapy
Betacoronavirus genetics
Coronavirus Infections pathology
Coronavirus Infections virology
Pneumonia, Viral pathology
Pneumonia, Viral virology
Respiratory System virology
Reverse Genetics methods
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4172
- Volume :
- 182
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 32526206
- Full Text :
- https://doi.org/10.1016/j.cell.2020.05.042