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

Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) is an unprecedented worldwide health problem that requires concerted and global approaches to stop the coronavirus 2019 (COVID-19) pandemic. Although SARS-CoV-2 primarily targets lung epithelium cells, there is growing evidence tha...

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Autores principales: Stanifer, Megan L., Kee, Carmon, Cortese, Mirko, Zumaran, Camila Metz, Triana, Sergio, Mukenhirn, Markus, Kraeusslich, Hans-Georg, Alexandrov, Theodore, Bartenschlager, Ralf, Boulant, Steeve
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303637/
https://www.ncbi.nlm.nih.gov/pubmed/32610043
http://dx.doi.org/10.1016/j.celrep.2020.107863
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author Stanifer, Megan L.
Kee, Carmon
Cortese, Mirko
Zumaran, Camila Metz
Triana, Sergio
Mukenhirn, Markus
Kraeusslich, Hans-Georg
Alexandrov, Theodore
Bartenschlager, Ralf
Boulant, Steeve
author_facet Stanifer, Megan L.
Kee, Carmon
Cortese, Mirko
Zumaran, Camila Metz
Triana, Sergio
Mukenhirn, Markus
Kraeusslich, Hans-Georg
Alexandrov, Theodore
Bartenschlager, Ralf
Boulant, Steeve
author_sort Stanifer, Megan L.
collection PubMed
description Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) is an unprecedented worldwide health problem that requires concerted and global approaches to stop the coronavirus 2019 (COVID-19) pandemic. Although SARS-CoV-2 primarily targets lung epithelium cells, there is growing evidence that the intestinal epithelium is also infected. Here, using both colon-derived cell lines and primary non-transformed colon organoids, we engage in the first comprehensive analysis of the SARS-CoV-2 life cycle in human intestinal epithelial cells (hIECs). Our results demonstrate that hIECs fully support SARS-CoV-2 infection, replication, and production of infectious de novo virus particles. We found that viral infection elicits an extremely robust intrinsic immune response where interferon-mediated responses are efficient at controlling SARS-CoV-2 replication and de novo virus production. Taken together, our data demonstrate that hIECs are a productive site of SARS-CoV-2 replication and suggest that the enteric phase of SARS-CoV-2 may participate in the pathologies observed in COVID-19 patients by contributing to increasing patient viremia and fueling an exacerbated cytokine response.
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spelling pubmed-73036372020-06-19 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, Hans-Georg Alexandrov, Theodore Bartenschlager, Ralf Boulant, Steeve Cell Rep Article Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) is an unprecedented worldwide health problem that requires concerted and global approaches to stop the coronavirus 2019 (COVID-19) pandemic. Although SARS-CoV-2 primarily targets lung epithelium cells, there is growing evidence that the intestinal epithelium is also infected. Here, using both colon-derived cell lines and primary non-transformed colon organoids, we engage in the first comprehensive analysis of the SARS-CoV-2 life cycle in human intestinal epithelial cells (hIECs). Our results demonstrate that hIECs fully support SARS-CoV-2 infection, replication, and production of infectious de novo virus particles. We found that viral infection elicits an extremely robust intrinsic immune response where interferon-mediated responses are efficient at controlling SARS-CoV-2 replication and de novo virus production. Taken together, our data demonstrate that hIECs are a productive site of SARS-CoV-2 replication and suggest that the enteric phase of SARS-CoV-2 may participate in the pathologies observed in COVID-19 patients by contributing to increasing patient viremia and fueling an exacerbated cytokine response. Cell Press 2020-06-19 /pmc/articles/PMC7303637/ /pubmed/32610043 http://dx.doi.org/10.1016/j.celrep.2020.107863 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Stanifer, Megan L.
Kee, Carmon
Cortese, Mirko
Zumaran, Camila Metz
Triana, Sergio
Mukenhirn, Markus
Kraeusslich, Hans-Georg
Alexandrov, Theodore
Bartenschlager, Ralf
Boulant, Steeve
Critical Role of Type III Interferon in Controlling SARS-CoV-2 Infection in Human Intestinal Epithelial Cells
title Critical Role of Type III Interferon in Controlling SARS-CoV-2 Infection in Human Intestinal Epithelial Cells
title_full Critical Role of Type III Interferon in Controlling SARS-CoV-2 Infection in Human Intestinal Epithelial Cells
title_fullStr Critical Role of Type III Interferon in Controlling SARS-CoV-2 Infection in Human Intestinal Epithelial Cells
title_full_unstemmed Critical Role of Type III Interferon in Controlling SARS-CoV-2 Infection in Human Intestinal Epithelial Cells
title_short Critical Role of Type III Interferon in Controlling SARS-CoV-2 Infection in Human Intestinal Epithelial Cells
title_sort critical role of type iii interferon in controlling sars-cov-2 infection in human intestinal epithelial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303637/
https://www.ncbi.nlm.nih.gov/pubmed/32610043
http://dx.doi.org/10.1016/j.celrep.2020.107863
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