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Authors:Ng et al 

Journal/ Pre-Print:bioRxiv 

TagsBioinformatics, Molecular biology 

Research Highlights  

  1. Identification of LTR16A1-ACE2 as the interferon-inducible isoform of ACE2 

  1. Tissue-specific expression of the isoforms, with the LTR16A1-ACE2 forming a decreasing gradient along the gastrointestinal tract 

  1. Canonical ACE2 is completely unresponsive to interferon 


Using de novo transcriptome assembly, Ng et al identified a previously unidentified isoform of ACE2, LTR16A1-ACE2. This isoform encodes a truncated ACE2 product, lacking the binding sites for SARS-CoV-2, and is interferon-inducible. The authors assessed the relative expression of ACE2 and LTR16A1-ACE2 across different tissue types using the TCGA and GTEx cohorts, as well as different cell lines. A tissue-specific expression, with the highest levels in the upper aerodigestive tract, was identified for LTR16A1-ACE2. The truncated form of the ACE2 receptor appears to be unstable and could not be detected at protein level in vitro. This study provides important information about interferon treatment of SARS-CoV-2 infection. 

Impact for SARS-CoV2/COVID19 research efforts  

Understand the immune response to SARS-CoV2/COVID19  

Study Type 

  • In silico study / bioinformatics study 

  • In vitro study 

Strengths and limitations of the paper 

Novelty: Novel truncated isoform of ACE2, which is interferon-inducible but lacks binding sites for SARS-CoV-2, identified 

Standing in the field:ACE2 had been suggested previously to be interferon-inducible (Ziegler et al., 2020), raising questions about interferon treatment of COVID-19 patients, which has been shown to improve outcomes of COVID-19 patients (Hung et al, 2020; Wang et al, 2020). This study shows that full-length ACE2 is not induced by interferon.  

Appropriate statistics:Statistics seem appropriate 

Viral model used:The study included one COVID-19 patient (for lung samples) 

Translatability:This study could potentially revisit previous claims about interferon treatments in COVID-19. 

Main limitations: They authors did not test whether or not SARS-CoV-2 infection stimulates LTR16A1-ACE2 expression (they only had one lung sample from a COVID-19 patient).