Y. Hou, K. Okuda, C. Edwards, D. R. Martinez, Takanori Asakura, K. Dinnon, Takafumi Kato, Rhianna E. Lee, B. Yount, T. Mascenik, G. Chen, K. Olivier, A. Ghio, L. V. Tse, S. Leist, Lisa E. Gralinski, A. Schäfer, H. Dang, R. Gilmore, S. Nakano, Ling Sun, M. Fulcher, A. Livraghi‐Butrico, N. Nicely, M. Cameron, C. Cameron, D. Kelvin, A. D. de Silva, D. Margolis, A. Markmann, L. Bartelt, R. Zumwalt, F. Martinez, S. Salvatore, A. Borczuk, P. Tata, Vishwaraj Sontake, A. Kimple, I. Jaspers, W. O’Neal, S. Randell, R. Boucher, R. Baric
Cell, 2020
Summary The mode of acquisition and causes for the variable clinical spectrum of COVID-19 remain unknown. We utilized a reverse genetics system to generate a GFP reporter virus to explore 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 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) vs 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.
Cited by 486 publications.
Field of study: Biology