PT  - JOURNAL ARTICLE
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 Austin
AU  - Bruce M. McManus
AU  - Gisli Jenkins
AU  - Karen Mossman
AU  - Kjetil Ask
AU  - Andrew C. Doxey
AU  - Jeremy A. Hirota
TI  - Gene expression and <em>in situ</em> protein profiling of candidate SARS-CoV-2 receptors in human airway epithelial cells and lung tissue
AID  - 10.1183/13993003.01123-2020
DP  - 2020 Jan 01
TA  - European Respiratory Journal
PG  - 2001123
4099  - http://erj.ersjournals.com/content/early/2020/07/06/13993003.01123-2020.short
4100  - http://erj.ersjournals.com/content/early/2020/07/06/13993003.01123-2020.full
AB  - In December 2019, SARS-CoV-2 emerged causing the COVID-19 pandemic. SARS-CoV, the agent responsible for the 2003 SARS outbreak, utilises ACE2 and 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 alternate 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. Our data suggest the presence of a mechanism dynamically regulating ACE2 expression in human lung or other receptors for SARS-CoV-2.