TY - JOUR T1 - Gene expression and <em>in situ</em> protein profiling of candidate SARS-CoV-2 receptors in human airway epithelial cells and lung tissue JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.01123-2020 VL - 56 IS - 3 SP - 2001123 AU - Jennifer A. Aguiar AU - Benjamin J-M. Tremblay AU - Michael J. Mansfield AU - Owen Woody AU - Briallen Lobb AU - Arinjay Banerjee AU - Abiram Chandiramohan AU - Nicholas Tiessen AU - Quynh Cao AU - Anna Dvorkin-Gheva AU - Spencer Revill AU - Matthew S. Miller AU - Christopher Carlsten AU - Louise Organ AU - Chitra Joseph AU - Alison John AU - Paul Hanson AU - Richard C. Austin AU - Bruce M. McManus AU - Gisli Jenkins AU - Karen Mossman AU - Kjetil Ask AU - Andrew C. Doxey AU - Jeremy A. Hirota Y1 - 2020/09/01 UR - http://erj.ersjournals.com/content/56/3/2001123.abstract N2 - In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, causing the coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV, the agent responsible for the 2003 SARS outbreak, utilises angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) host molecules for viral entry. ACE2 and TMPRSS2 have recently been implicated in SARS-CoV-2 viral infection. Additional host molecules including ADAM17, cathepsin L, CD147 and GRP78 may also function as receptors for SARS-CoV-2.To determine the expression and in situ localisation of candidate SARS-CoV-2 receptors in the respiratory mucosa, we analysed gene expression datasets from airway epithelial cells of 515 healthy subjects, gene promoter activity analysis using the FANTOM5 dataset containing 120 distinct sample types, single cell RNA sequencing (scRNAseq) of 10 healthy subjects, proteomic datasets, immunoblots on multiple airway epithelial cell types, and immunohistochemistry on 98 human lung samples.We demonstrate absent to low ACE2 promoter activity in a variety of lung epithelial cell samples and low ACE2 gene expression in both microarray and scRNAseq datasets of epithelial cell populations. Consistent with gene expression, rare ACE2 protein expression was observed in the airway epithelium and alveoli of human lung, confirmed with proteomics. We present confirmatory evidence for the presence of TMPRSS2, CD147 and GRP78 protein in vitro in airway epithelial cells and confirm broad in situ protein expression of CD147 and GRP78 in the respiratory mucosa.Collectively, our data suggest the presence of a mechanism dynamically regulating ACE2 expression in human lung, perhaps in periods of SARS-CoV-2 infection, and also suggest that alternative receptors for SARS-CoV-2 exist to facilitate initial host cell infection.ACE2 gene and protein expression is low to absent in airway and alveolar epithelial cells in human lungs. This study suggests the presence of a mechanism dynamically regulating ACE2 expression in human lung or other receptors for SARS-CoV-2. https://bit.ly/3f85R1I ER -