Yixuan J. Hou, Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Kenichi Okuda, Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Caitlin E. Edwards, Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
David R. Martinez, Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Takanori Asakura, Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Kenneth H. Dinnon, Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Takafumi Kato, Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Rhianna E. Lee, Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Boyd L. Yount, Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Teresa M. Mascenik, Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Gang Chen, Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Kenneth N. Olivier, Laboratory of Chronic Airway Infection, Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
Andrew Ghio, National Health and Environmental Effects Research Laboratory, Environmental Protection Agency, Chapel Hill, NC, USA
Longping V. Tse, Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Sarah R. Leist, Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Lisa E. Gralinski, Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Alexandra Schäfer, Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Hong Dang, Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Rodney Gilmore, Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Satoko Nakano, Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Ling Sun, Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
M Leslie Fulcher, Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Alessandra Livraghi-Butrico, Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Nathan I. Nicely, Protein Expression and Purification Core, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Mark Cameron, Department of Population and Quantitative Health Science, Case Western Reserve University, Cleveland, OH, USA
Cheryl Cameron, Department of Nutrition, Case Western Reserve University, Cleveland, OH, USA
David J. Kelvin, Department of Microbiology and Immunology, Canadian Center for Vaccinology, Dalhousie University, Halifax, NS, Canada; Laboratory of Immunology, Shantou University Medical College, Shantou, Guangdong, China
Aravinda de Silva, Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
David M. Margolis, Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; HIV Cure Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Alena Markmann, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Luther Bartelt, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Ross Zumwalt, Department of Pathology, University of New Mexico, Albuquerque, NM, USA
Fernando J. Martinez, Division of Pulmonary and Critical Care Medicine, Joan & Sanford I. Weill Medical College of Cornell University, New York, NY, USA
Steven P. Salvatore, Department of Pathology, Joan & Sanford I. Weill Medical College of Cornell University, New York, NY, USA
Alain Borczuk, Department of Pathology, Joan & Sanford I. Weill Medical College of Cornell University, New York, NY, USA
Purushothama R. Tata, Department of Cell Biology, Regeneration Next Initiative, Duke University Medical Center, Durham, NC, USA
Vishwaraj Sontake, Department of Cell Biology, Regeneration Next Initiative, Duke University Medical Center, Durham, NC, USA
Adam Kimple, Department of Otolaryngology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Ilona Jaspers, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Wanda K. O'Neal, Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Scott H. Randell, Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Richard C. Boucher, Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAFollow
Ralph S. Baric, Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAFollow

Document Type

Article

Publication Date

7-23-2020

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.

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