Journal
CELL
Volume 182, Issue 2, Pages 429-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2020.05.042
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Funding
- National Allergy and Infectious Disease (NIAID), National Institution of Health (NIH) [U19-AI100625, R01-AI089728, U01-AI14964]
- National Heart, Lung, and Blood Institute (NHLBI), NIH [UH3-HL123645, P01-HL110873, R01-HL136961, P30-DK065988-13, P01-HL108808]
- Cystic Fibrosis Foundation [OKUDA10I0]
- Cystic Fibrosis Research Incorporation
- NIH NIAID [T32 AI007151]
- Burroughs Wellcome Fund Postdoctoral Enrichment Program Award
- American Lung Association [RT-57362]
- National Center for Advancing Translational Sciences, NIH [KL2TR002490]
- NHLBI/NIH [R00HL127181, R01HL146557]
- Regeneration Next Initiative at Duke University
- NCI Center Core Support Grant [5P30CA016086-41]
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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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