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Authors: Stanifer et al.

Link to paper: https://doi.org/10.1101/2020.04.24.059667.

Journal/ Pre-Print: www.biorxiv.com

Tags: Virolgy, Immunology/Immunity, Gut, Stem Cells, Interferons

Research Highlights 

1. Intestinal epithelial cells are a productive site for enteric SARS-CoV2- replication and increased viremia leading to increased cytokine response.

2. SARS-CoV-2 infection elicited a robust intrinsic Type I and Type III interferon response in colonic cell lines and colonic epithelial organoids.

3. Type III Interferon mediated antiviral response was significantly more efficient than Type I interferon in the intestinal epithelium.

Summary 

This study demonstrates the enteric phase of the SARS-CoV-2 lifecycle using primary undifferentiated human colonic organoids and colon-derived cell lines. Exogenous administration of both type I and type III IFN, induced an antiviral state in the virus infected cells. Interestingly, infection by SARS-CoV-2 lead to the production of intrinsic type III IFN but not type I IFN. An increase in viral load was observed in the absence of type III IFN signalling demonstrated by the genetic deletion of type III IFN receptor. Overall, the study demonstrates that the gut epithelium is an active site for SARS-CoV-2 replication and highlights the central role of type III IFN in mediating epithelial anti-viral defence.

Impact for SARS-CoV2/COVID19 research efforts

- Understand the immune response to SARS-CoV2/COVID19

- Understand the virology and/or cell biology of SARS-CoV2/COVID19

- Inhibit of SARS-CoV2/COVID19 transmission

Study Type

· In vitro study: T84 and CaCo-2 cell lines used

· In vivo study: Human colonic organoids used

Strengths and limitations of the paper

Novelty: Type III IFN mediates intestinal epithelial antiviral response against SARS-CoV-2

Standing in the field: There are other publications supporting 1) the protective role of type III IFN against SARS-CoV-2, rotaviruses, noroviruses, etc and 2) type III IFN as a key player in epithelial antiviral defense

Appropriate statistics: Yes, appropriate statistics used.

Viral model used: BavPat1 strain obtained from Charite Hospital, Berlin was used

Translatability: Colonic organoid was derived from only 2 healthy donors. Not enough data to demonstrate translatability potential.

Main limitations:

1. Only 10% of colonic cells were infected by the virus. ACE2 receptor expression was shown to be abundant in the small intestine. It would have been beneficial to see if SARS-CoV-2 induces similar interferon response in the small intestine.

2. The origin of SARS-CoV-2 replication site is still unclear

3. No protein read outs of IFN

4. Biased (other cytokines and chemokines) /no mechanisms (which ISG genes?)

5. dsRNA IF read out neglected throughout paper