ACE2 localizes to the respiratory cilia and is not increased by ACE inhibitors or ARBs.
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Lee IT
Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
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Nakayama T
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
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Wu CT
Baxter Laboratory, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, USA.
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Goltsev Y
Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
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Jiang S
Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
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Gall PA
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
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Liao CK
Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.
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Shih LC
Department of Otorhinolaryngology, China Medical University Hospital, Taichung, Taiwan.
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Schürch CM
Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
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McIlwain DR
Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
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Chu P
Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
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Borchard NA
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
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Zarabanda D
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
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Dholakia SS
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
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Yang A
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
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Kim D
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
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Chen H
Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
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Kanie T
Baxter Laboratory, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, USA.
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Lin CD
Department of Otorhinolaryngology, China Medical University Hospital, Taichung, Taiwan.
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Tsai MH
Department of Otorhinolaryngology, China Medical University Hospital, Taichung, Taiwan.
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Phillips KM
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
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Kim R
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
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Overdevest JB
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
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Tyler MA
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
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Yan CH
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
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Lin CF
Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.
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Lin YT
Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.
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Bau DT
Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
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Tsay GJ
School of Medicine, China Medical University, Taichung, Taiwan.
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Patel ZM
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
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Tsou YA
Department of Otorhinolaryngology, China Medical University Hospital, Taichung, Taiwan.
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Tzankov A
Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
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Matter MS
Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
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Tai CJ
Department of Otorhinolaryngology, China Medical University Hospital, Taichung, Taiwan.
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Yeh TH
Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.
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Hwang PH
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
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Nolan GP
Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA. gnolan@stanford.edu.
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Nayak JV
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
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Jackson PK
Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
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Published in:
- Nature communications. - 2020
English
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.
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gold
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https://folia.unifr.ch/global/documents/189254
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