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SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract.
Hou, Yixuan J; Okuda, Kenichi; Edwards, Caitlin E; Martinez, David R; Asakura, Takanori; Dinnon, Kenneth H; Kato, Takafumi; Lee, Rhianna E; Yount, Boyd L; Mascenik, Teresa M; Chen, Gang; Olivier, Kenneth N; Ghio, Andrew; Tse, Longping V; Leist, Sarah R; Gralinski, Lisa E; Schäfer, Alexandra; Dang, Hong; Gilmore, Rodney; Nakano, Satoko; Sun, Ling; Fulcher, M Leslie; Livraghi-Butrico, Alessandra; Nicely, Nathan I; Cameron, Mark; Cameron, Cheryl; Kelvin, David J; de Silva, Aravinda; Margolis, David M; Markmann, Alena; Bartelt, Luther; Zumwalt, Ross; Martinez, Fernando J; Salvatore, Steven P; Borczuk, Alain; Tata, Purushothama R; Sontake, Vishwaraj; Kimple, Adam; Jaspers, Ilona; O'Neal, Wanda K; Randell, Scott H; Boucher, Richard C; Baric, Ralph S.
  • Hou YJ; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Okuda K; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Edwards CE; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Martinez DR; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Asakura T; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Dinnon KH; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Kato T; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Lee RE; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Yount BL; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Mascenik TM; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Chen G; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Olivier KN; Laboratory of Chronic Airway Infection, Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Ghio A; National Health and Environmental Effects Research Laboratory, Environmental Protection Agency, Chapel Hill, NC, USA.
  • Tse LV; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Leist SR; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Gralinski LE; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Schäfer A; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Dang H; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Gilmore R; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Nakano S; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Sun L; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Fulcher ML; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Livraghi-Butrico A; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Nicely NI; Protein Expression and Purification Core, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Cameron M; Department of Population and Quantitative Health Science, Case Western Reserve University, Cleveland, OH, USA.
  • Cameron C; Department of Nutrition, Case Western Reserve University, Cleveland, OH, USA.
  • Kelvin DJ; Department of Microbiology and Immunology, Canadian Center for Vaccinology, Dalhousie University, Halifax, NS, Canada; Laboratory of Immunology, Shantou University Medical College, Shantou, Guangdong, China.
  • de Silva A; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Margolis DM; 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.
  • Markmann A; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Bartelt L; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Zumwalt R; Department of Pathology, University of New Mexico, Albuquerque, NM, USA.
  • Martinez FJ; Division of Pulmonary and Critical Care Medicine, Joan & Sanford I. Weill Medical College of Cornell University, New York, NY, USA.
  • Salvatore SP; Department of Pathology, Joan & Sanford I. Weill Medical College of Cornell University, New York, NY, USA.
  • Borczuk A; Department of Pathology, Joan & Sanford I. Weill Medical College of Cornell University, New York, NY, USA.
  • Tata PR; Department of Cell Biology, Regeneration Next Initiative, Duke University Medical Center, Durham, NC, USA.
  • Sontake V; Department of Cell Biology, Regeneration Next Initiative, Duke University Medical Center, Durham, NC, USA.
  • Kimple A; Department of Otolaryngology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Jaspers I; Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • O'Neal WK; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Randell SH; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Boucher RC; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: richard_boucher@med.unc.edu.
  • Baric RS; 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, USA. Electronic address: rbaric@email.unc.edu.
Cell ; 182(2): 429-446.e14, 2020 07 23.
Article in English | MEDLINE | ID: covidwho-381993
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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Respiratory System / Coronavirus Infections / Reverse Genetics / Betacoronavirus Type of study: Prognostic study / Randomized controlled trials Language: English Journal: Cell Year: 2020 Document Type: Article Affiliation country: J.cell.2020.05.042

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Respiratory System / Coronavirus Infections / Reverse Genetics / Betacoronavirus Type of study: Prognostic study / Randomized controlled trials Language: English Journal: Cell Year: 2020 Document Type: Article Affiliation country: J.cell.2020.05.042