ACE2 localizes to the respiratory cilia and is not increased by ACE inhibitors or ARBs

Ivan T. Lee, Tsuguhisa Nakayama, Chien-Ting Wu, Yury Goltsev, Sizun Jiang, Phillip A. Gall, Chun-Kang Liao, Liang-Chun Shih, Christian M. Schürch, David R. McIlwain, Pauline Chu, Nicole A. Borchard, David Zarabanda, Sachi S. Dholakia, Angela Yang, Dayoung Kim, Han Chen, Tomoharu Kanie, Chia- Der Lin, Ming-Hsui Tsai, Katie M. Phillips, Raymond Kim, Jonathan B. Overdevest, Matthew A. Tyler, Carol H. Yan, Chih-Feng Lin, Yi-Tsen Lin, Da-Tian Bau, Gregory J. Tsay, Zara M. Patel, Yung-An Tsou, Alexandar Tzankov, Matthias S. Matter, Chih-Jaan Tai, Te-Huei Yeh, Peter H. Hwang, Garry P. Nolan (), Jayakar V. Nayak and Peter K. Jackson
Additional contact information
Ivan T. Lee: Stanford University School of Medicine
Tsuguhisa Nakayama: Stanford University School of Medicine
Chien-Ting Wu: Stanford University School of Medicine
Yury Goltsev: Stanford University School of Medicine
Sizun Jiang: Stanford University School of Medicine
Phillip A. Gall: Stanford University School of Medicine
Chun-Kang Liao: National Taiwan University Hospital
Liang-Chun Shih: China Medical University Hospital
Christian M. Schürch: Stanford University School of Medicine
David R. McIlwain: Stanford University School of Medicine
Pauline Chu: Stanford University School of Medicine
Nicole A. Borchard: Stanford University School of Medicine
David Zarabanda: Stanford University School of Medicine
Sachi S. Dholakia: Stanford University School of Medicine
Angela Yang: Stanford University School of Medicine
Dayoung Kim: Stanford University School of Medicine
Han Chen: Stanford University School of Medicine
Tomoharu Kanie: Stanford University School of Medicine
Chia- Der Lin: China Medical University Hospital
Ming-Hsui Tsai: China Medical University Hospital
Katie M. Phillips: Stanford University School of Medicine
Raymond Kim: Stanford University School of Medicine
Jonathan B. Overdevest: Stanford University School of Medicine
Matthew A. Tyler: Stanford University School of Medicine
Carol H. Yan: Stanford University School of Medicine
Chih-Feng Lin: National Taiwan University Hospital
Yi-Tsen Lin: National Taiwan University Hospital
Da-Tian Bau: China Medical University
Gregory J. Tsay: China Medical University
Zara M. Patel: Stanford University School of Medicine
Yung-An Tsou: China Medical University Hospital
Alexandar Tzankov: University Hospital Basel, University of Basel
Matthias S. Matter: University Hospital Basel, University of Basel
Chih-Jaan Tai: China Medical University Hospital
Te-Huei Yeh: National Taiwan University Hospital
Peter H. Hwang: Stanford University School of Medicine
Garry P. Nolan: Stanford University School of Medicine
Jayakar V. Nayak: Stanford University School of Medicine
Peter K. Jackson: Stanford University School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract The coronavirus SARS-CoV-2 is the causative agent of the ongoing severe acute respiratory disease pandemic COVID-19. Tissue and cellular tropism is one key to understanding the pathogenesis of SARS-CoV-2. We investigate the expression and subcellular localization of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), within the upper (nasal) and lower (pulmonary) respiratory tracts of human donors using a diverse panel of banked tissues. Here, we report our discovery that the ACE2 receptor protein robustly localizes within the motile cilia of airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during host respiratory transmission. We further determine whether ciliary ACE2 expression in the upper airway is influenced by patient demographics, clinical characteristics, comorbidities, or medication use, and show the first mechanistic evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) does not increase susceptibility to SARS-CoV-2 infection through enhancing the expression of ciliary ACE2 receptor. These findings are crucial to our understanding of the transmission of SARS-CoV-2 for prevention and control of this virulent pathogen.

Date: 2020
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DOI: 10.1038/s41467-020-19145-6

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