Critical Role of Type III Interferon in Controlling SARS-CoV-2 Infection in Human Intestinal Epithelial Cells

Stanifer, Megan L.; Kee, Carmon; Cortese, Mirko; Zumaran, Camila Metz; Triana, Sergio; Mukenhirn, Markus; Kraeusslich, H.-G.; Alexandrov, Theodore; Bartenschlager, Ralf; Boulant, Steeve

doi:10.1016/j.celrep.2020.107863

Cited by 302 publications

(413 citation statements)

References 42 publications

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“…All cell lines were successfully infected with SARS-CoV-2 ( Figure 5B, Table S2D), but ACE2 expression was not affected by infection in any cell line tested ( Figure 5A, Table S2D). Induction of dACE2 expression tracked with previously reported SARS-CoV-2 infectivity rates in these cells 23 Table S2D). We performed a similar analysis in human colon and ileum organoid cultures derived from two donors.…”

Section: Dace2 Is Induced By Sars-cov-2 In Vitrosupporting

confidence: 79%

“…We performed a similar analysis in human colon and ileum organoid cultures derived from two donors. There was more variability in expression of the three genes tested but, overall, the expression of dACE2 and IFIT1 but not ACE2 was significantly induced by SARS-CoV-2 infection ( Figure 5C, Table S2E), despite comparable SARS-CoV-2 infection load ( Figure 5D, Table S2E), and a similar infection rate (10% of the cells) 23 . These results confirm that dACE2 is inducible by SARS-CoV-2 infection.…”

Section: Dace2 Is Induced By Sars-cov-2 In Vitromentioning

confidence: 95%

“…In most cell lines tested, dACE2 but not ACE2 was strongly upregulated by SeV infection (Figure 2B, C). To directly address whether IFN was responsible for the induced expression of dACE2, we performed expression analysis in primary normal human bronchial epithelial (NHBE) cells 22 and human intestinal (colon and ileum) organoid cultures 23 . In NHBE cells from 5 healthy donors, baseline expression levels of dACE2 and ACE2 were comparable, but only dACE2 was significantly induced by treatment with IFN-α or IFN-λ3 ( Figure 2D, Table S2B).…”

Section: Dace2 Is Induced By In Vitro Treatment With Ifnsmentioning

confidence: 99%

“…The previously described 22 approved by the Ethics Commission of the University Hospital Heidelberg. Organoids were generated from these tissues as previously described 23 .…”

Section: Cellsmentioning

confidence: 99%

“…Infections with SARS-CoV-2 in colon cancer cell lines (Caco2 and T84) and lung cancer cell line (Calu3) and colon and ileum organoid cultures were previously described 23 . Briefly, the infections were performed using the MOI=1 for cell lines.…”

Section: Cells Listed Inmentioning

confidence: 99%

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Interferons and viruses induce a novel primate-specific isoform dACE2 and not the SARS-CoV-2 receptor ACE2

Onabajo

Banday

Yan

et al. 2020

Preprint

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes COVID-19, utilizes angiotensin-converting enzyme 2 (ACE2) for entry into target cells. ACE2 has been proposed as an interferon-stimulated gene (ISG). Thus, interferon-induced variability in ACE2 expression levels could be important for susceptibility to COVID-19 or its outcomes. Here, we report the discovery of a novel, primate-specific isoform of ACE2, which we designate as deltaACE2 (dACE2). We demonstrate that dACE2, but not ACE2, is an ISG. In vitro, dACE2, which lacks 356 N-terminal amino acids, was non-functional in binding the SARS-CoV-2 spike protein and as a carboxypeptidase. Our results reconcile current knowledge on ACE2 expression and suggest that the ISG-type induction of dACE2 in IFN-high conditions created by treatments, inflammatory tumor microenvironment, or viral co-infections is unlikely to affect the cellular entry of SARS-CoV-2 and promote infection.

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Section: Dace2 Is Induced By Sars-cov-2 In Vitrosupporting

confidence: 79%

Section: Dace2 Is Induced By Sars-cov-2 In Vitromentioning

confidence: 95%

Section: Dace2 Is Induced By In Vitro Treatment With Ifnsmentioning

confidence: 99%

“…The previously described 22 approved by the Ethics Commission of the University Hospital Heidelberg. Organoids were generated from these tissues as previously described 23 .…”

Section: Cellsmentioning

confidence: 99%

Section: Cells Listed Inmentioning

confidence: 99%

See 3 more Smart Citations

Interferons and viruses induce a novel primate-specific isoform dACE2 and not the SARS-CoV-2 receptor ACE2

Onabajo

Banday

Yan

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

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Human Organoids and Organs‐on‐Chips for Addressing COVID‐19 Challenges

Wang

Qin

2022

Advanced Science

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Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses an imminent threat to our lives. Although animal models and monolayer cell cultures are utilized for pathogenesis studies and the development of COVID-19 therapeutics, models that can more accurately reflect human-relevant responses to this novel virus are still lacking. Stem cell organoids and bioengineered organs-on-chips have emerged as two cutting-edge technologies used to construct biomimetic in vitro three-dimensional (3D) tissue or organ models. In this review, the key features of these two model systems that allow them to recapitulate organ physiology and function are introduced. The recent progress of these technologies for virology research is summarized and their utility in meeting the COVID-19 pandemic is highlighted. Future opportunities and challenges in the development of advanced human organ models and their potential to accelerate translational applications to provide vaccines and therapies for COVID-19 and other emerging epidemics are also discussed.

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3D printed human organoids: High throughput system for drug screening and testing in current COVID‐19 pandemic

Parihar

Pandita

Khan

2022

Biotech & Bioengineering

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In the current pandemic, scenario the world is facing a huge shortage of effective drugs and other prophylactic medicine to treat patients which created havoc in several countries with poor resources. With limited demand and supply of effective drugs, researchers rushed to repurpose the existing approved drugs for the treatment of COVID‐19. The process of drug screening and testing is very costly and requires several steps for validation and treatment efficacy evaluation ranging from in‐vitro to in‐vivo setups. After these steps, a clinical trial is mandatory for the evaluation of treatment efficacy and side effects in humans. These processes enhance the overall cost and sometimes the lead molecule show adverse effects in humans and the trial ends up in the final stages. Recently with the advent of three‐dimensional (3D) organoid culture which mimics the human tissue exactly the process of drug screening and testing can be done in a faster and cost‐effective manner. Further 3D organoids prepared from stems cells taken from individuals can be beneficial for personalized drug therapy which could save millions of lives. This review discussed approaches and techniques for the synthesis of 3D‐printed human organoids for drug screening. The key findings of the usage of organoids for personalized medicine for the treatment of COVID‐19 have been discussed. In the end, the key challenges for the wide applicability of human organoids for drug screening with prospects of future orientation have been included.

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Critical Role of Type III Interferon in Controlling SARS-CoV-2 Infection in Human Intestinal Epithelial Cells

Abstract: Highlights d Human intestinal epithelium cells (hIECs) can be infected by SARS-CoV-2 d hIECs support SARS-CoV-2 replication and produce de novo viruses d SARS-CoV-2 infection can be controlled in hIECs by type I and III interferons

Cited by 302 publications

References 42 publications

Interferons and viruses induce a novel primate-specific isoform dACE2 and not the SARS-CoV-2 receptor ACE2

Interferons and viruses induce a novel primate-specific isoform dACE2 and not the SARS-CoV-2 receptor ACE2

Human Organoids and Organs‐on‐Chips for Addressing COVID‐19 Challenges

3D printed human organoids: High throughput system for drug screening and testing in current COVID‐19 pandemic

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