SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract | Zendy

Yixuan J. Hou | Zendy; Kenichi Okuda | Zendy; Caitlin E. Edwards | Zendy; David R. Martinez | Zendy; Takanori Asakura | Zendy; Kenneth H. Din | Zendy; Takafumi Kato | Zendy; Rhianna E. Lee | Zendy; Boyd L. Yount | Zendy; Teresa Mascenik | Zendy; Gang Chen | Zendy; Kenneth N. Olivier | Zendy; Andrew J. Ghio | Zendy; Longping V. Tse | Zendy; Sarah R. Leist | Zendy; Lisa E. Gralinski | Zendy; Alexandra Schäfer | Zendy; Hong Dang | Zendy; Rodney C. Gilmore | Zendy; Satoko Nakano | Zendy; Ling Sun | Zendy; M. Leslie Fulcher | Zendy; Alessandra Livraghi-Butrico | Zendy; Nathan I. Nicely | Zendy; Mark J. Cameron | Zendy; Cheryl Cameron | Zendy; David J. Kelvin | Zendy; Aravinda de Silva | Zendy; David M. Margolis | Zendy; Alena J. Markmann | Zendy; Luther A. Bartelt | Zendy; Ross E. Zumwalt | Zendy; Fernando J. Martínez | Zendy; Steven Salvatore | Zendy; Alain Borczuk | Zendy; Purushothama Rao Tata | Zendy; Vishwaraj Sontake | Zendy; Adam J. Kimple | Zendy; Ilona Jaspers | Zendy; Wanda K. O’Neal | Zendy; Scott H. Randell | Zendy; Richard C. Boucher | Zendy; Ralph S. Baric | Zendy

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SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract

Author(s) -

Yixuan J. Hou,

Kenichi Okuda,

Caitlin E. Edwards,

David R. Martinez,

Takanori Asakura,

Kenneth H. Din,

Takafumi Kato,

Rhianna E. Lee,

Boyd L. Yount,

Teresa Mascenik,

Gang Chen,

Kenneth N. Olivier,

Andrew J. Ghio,

Longping V. Tse,

Sarah R. Leist,

Lisa E. Gralinski,

Alexandra Schäfer,

Hong Dang,

Rodney C. Gilmore,

Satoko Nakano,

Ling Sun,

M. Leslie Fulcher,

Alessandra Livraghi-Butrico,

Nathan I. Nicely,

Mark J. Cameron,

Cheryl Cameron,

David J. Kelvin,

Aravinda de Silva,

David M. Margolis,

Alena J. Markmann,

Luther A. Bartelt,

Ross E. Zumwalt,

Fernando J. Martínez,

Steven Salvatore,

Alain Borczuk,

Purushothama Rao Tata,

Vishwaraj Sontake,

Adam J. Kimple,

Ilona Jaspers,

Wanda K. O’Neal,

Scott H. Randell,

Richard C. Boucher,

Ralph S. Baric

Publication year - 2020

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2020.05.042

Subject(s) - biology , respiratory tract , virology , covid-19 , genetics , reverse genetics , respiratory system , genome , gene , disease , infectious disease (medical specialty) , pathology , outbreak , medicine , anatomy

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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