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. Understanding how SARS-CoV-2 gains initial entry into the human body is a key step towards the development of prophylaxes and therapeutics for COVID-19. Here, the authors show that ACE2, the receptor for SARS-CoV-2, is abundantly expressed in the motile cilia of the human nasal and respiratory tract and is not affected by the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers.
【저자키워드】 SARS-CoV-2, viral infection, Respiratory tract diseases, 【초록키워드】 COVID-19, ACE2, pandemic, Clinical characteristics, SARS-COV-2 infection, susceptibility, Comorbidities, ACE2 receptor, Transmission, nasal, coronavirus SARS-CoV-2, angiotensin-converting enzyme 2, airway, pathogen, Patient, understanding, respiratory tract, receptor, medication, ACE2 expression, expression, ACEi, angiotensin-converting enzyme inhibitor, Evidence, ARBs, acute respiratory disease, airway epithelial cells, demographics, Motile cilia, tissues, blocker, blockers, subcellular localization, virulent, transmission of SARS-CoV-2, pathogenesis of SARS-CoV-2, Host, cellular tropism, initial, SARS-CoV-2 viral, determine, not affected, subcellular, abundantly expressed, ACE2 receptor protein, ciliary, human donor, the SARS-CoV-2, 【제목키워드】 ACE2, ARB, ACE inhibitor, respiratory cilia,