New Paper (Other): SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues

[dziakj1]

Title: SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues

General Information

Please paste a link to the paper or a citation here:

Link: https://doi.org/10.1016/j.cell.2020.04.035

What is the paper's Manubot-style citation?

Citation: doi:10.1016/j.cell.2020.04.035

Is this paper primarily relevant to Background or Pathogenesis?

• [ ] Background
• [x] Pathogenesis
• [ ] Methods

Please list some keywords (3-10) that help identify the relevance of this paper to COVID-19

• interferon
• ACE2
• RNA sequencing
• epithelial cells

Which areas of expertise are particularly relevant to the paper?

• [x] virology
• [ ] epidemiology
• [ ] biostatistics
• [x] immunology
• [x] pharmacology
• [ ] other:

Summary

I am sorry that I don't have the background in biology to intelligently summarize this paper.
It is briefly summarized by Nature.com at https://www.nature.com/articles/d41586-020-00502-w under the header "29 April — SARS-CoV-2 might invade by hijacking its host’s immune defences" but the summary there doesn't seem to be completely representing the paper. The abstract of the paper is : "There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) which causes the disease COVID-19. SARSCoV- 2 spike (S)-protein binds ACE2, and in concert with host proteases, principally TMPRSS2, promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues, and the factors that regulate ACE2 expression, remain unknown. Here, we leverage human, non-human primate, and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 amongst tissue-resident cell subsets. We identify ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells. Strikingly, we discover that ACE2 is a human interferon-stimulated gene (ISG) in vitro using airway epithelial cells, and extend our findings to in vivo viral infections. Our data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection."

Suggested questions to answer about each paper:

• What did they analyze?
• What methods did they use?
• Does this paper study COVID-19, SARS-CoV-2, or a related disease and/or virus?
• What is the main finding (or a few main takeaways)?
• What does this paper tell us about the background and/or diagnostics/therapeutics for COVID-19 / SARS-CoV-2?
• Do you have any concerns about methodology or the interpretation of these results beyond this analysis?

Any comments or notes?

[dziakj1]

Their summary of their results in the discussion: "Here, we utilize scRNA-seq across various barrier tissues and model organisms to identify the potential initial cellular targets of SARS-CoV-2 infection. To review the data presented: 1) we find that expression of the cellular entry receptor for SARS-CoV-2, ACE2, is primarily restricted to type II pneumocytes in the lung, absorptive enterocytes within the gut, and goblet secretory cells of the nasal mucosa; 2) ACE2 and TMPRSS2 co-expression in respiratory tissues is consistently found only among a rare subset of epithelial cells; 3) we observe similarities in the cellular identities and frequencies of putative SARS-CoV-2 target cells across human and NHP cohorts; 4) we observe increased expression of ACE2 during SHIV and TB infection of NHPs, and HIV/TB coinfection and influenza infection of humans relative to matched controls, but caution that none of the datasets presented here were designed to answer this specific query." However, they follow this with a caveat about the difficulties of "scRNA-seq data for low abundance transcripts like ACE2 and TMPRSS2" because of "detection inefficiencies."