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Increased Sensitivity of SARS-CoV-2 to Type III Interferon in Human Intestinal Epithelial Cells

The coronavirus SARS-CoV-2 caused the COVID-19 global pandemic leading to 5.3 million deaths worldwide as of December 2021. The human intestine was found to be a major viral target which could have a strong impact on virus spread and pathogenesis since it is one of the largest organs. While type I i...

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Autores principales: Metz-Zumaran, Camila, Kee, Carmon, Doldan, Patricio, Guo, Cuncai, Stanifer, Megan L., Boulant, Steeve
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9006957/
https://www.ncbi.nlm.nih.gov/pubmed/35262371
http://dx.doi.org/10.1128/jvi.01705-21
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author Metz-Zumaran, Camila
Kee, Carmon
Doldan, Patricio
Guo, Cuncai
Stanifer, Megan L.
Boulant, Steeve
author_facet Metz-Zumaran, Camila
Kee, Carmon
Doldan, Patricio
Guo, Cuncai
Stanifer, Megan L.
Boulant, Steeve
author_sort Metz-Zumaran, Camila
collection PubMed
description The coronavirus SARS-CoV-2 caused the COVID-19 global pandemic leading to 5.3 million deaths worldwide as of December 2021. The human intestine was found to be a major viral target which could have a strong impact on virus spread and pathogenesis since it is one of the largest organs. While type I interferons (IFNs) are key cytokines acting against systemic virus spread, in the human intestine type III IFNs play a major role by restricting virus infection and dissemination without disturbing homeostasis. Recent studies showed that both type I and III IFNs can inhibit SARS-CoV-2 infection, but it is not clear whether one IFN controls SARS-CoV-2 infection of the human intestine better or with a faster kinetics. In this study, we could show that type I and III IFNs both possess antiviral activity against SARS-CoV-2 in human intestinal epithelial cells (hIECs); however, type III IFN is more potent. Shorter type III IFN pretreatment times and lower concentrations were required to efficiently reduce virus load compared to type I IFNs. Moreover, type III IFNs significantly inhibited SARS-CoV-2 even 4 h postinfection and induced a long-lasting antiviral effect in hIECs. Importantly, the sensitivity of SARS-CoV-2 to type III IFNs was virus specific since type III IFN did not control VSV infection as efficiently. Together, these results suggest that type III IFNs have a higher potential for IFN-based treatment of SARS-CoV-2 intestinal infection compared to type I IFNs. IMPORTANCE SARS-CoV-2 infection is not restricted to the respiratory tract and a large number of COVID-19 patients experience gastrointestinal distress. Interferons are key molecules produced by the cell to combat virus infection. Here, we evaluated how two types of interferons (type I and III) can combat SARS-CoV-2 infection of human gut cells. We found that type III interferons were crucial to control SARS-CoV-2 infection when added both before and after infection. Importantly, type III interferons were also able to produce a long-lasting effect, as cells were protected from SARS-CoV-2 infection up to 72 h posttreatment. This study suggested an alternative treatment possibility for SARS-CoV-2 infection.
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spelling pubmed-90069572022-04-14 Increased Sensitivity of SARS-CoV-2 to Type III Interferon in Human Intestinal Epithelial Cells Metz-Zumaran, Camila Kee, Carmon Doldan, Patricio Guo, Cuncai Stanifer, Megan L. Boulant, Steeve J Virol Pathogenesis and Immunity The coronavirus SARS-CoV-2 caused the COVID-19 global pandemic leading to 5.3 million deaths worldwide as of December 2021. The human intestine was found to be a major viral target which could have a strong impact on virus spread and pathogenesis since it is one of the largest organs. While type I interferons (IFNs) are key cytokines acting against systemic virus spread, in the human intestine type III IFNs play a major role by restricting virus infection and dissemination without disturbing homeostasis. Recent studies showed that both type I and III IFNs can inhibit SARS-CoV-2 infection, but it is not clear whether one IFN controls SARS-CoV-2 infection of the human intestine better or with a faster kinetics. In this study, we could show that type I and III IFNs both possess antiviral activity against SARS-CoV-2 in human intestinal epithelial cells (hIECs); however, type III IFN is more potent. Shorter type III IFN pretreatment times and lower concentrations were required to efficiently reduce virus load compared to type I IFNs. Moreover, type III IFNs significantly inhibited SARS-CoV-2 even 4 h postinfection and induced a long-lasting antiviral effect in hIECs. Importantly, the sensitivity of SARS-CoV-2 to type III IFNs was virus specific since type III IFN did not control VSV infection as efficiently. Together, these results suggest that type III IFNs have a higher potential for IFN-based treatment of SARS-CoV-2 intestinal infection compared to type I IFNs. IMPORTANCE SARS-CoV-2 infection is not restricted to the respiratory tract and a large number of COVID-19 patients experience gastrointestinal distress. Interferons are key molecules produced by the cell to combat virus infection. Here, we evaluated how two types of interferons (type I and III) can combat SARS-CoV-2 infection of human gut cells. We found that type III interferons were crucial to control SARS-CoV-2 infection when added both before and after infection. Importantly, type III interferons were also able to produce a long-lasting effect, as cells were protected from SARS-CoV-2 infection up to 72 h posttreatment. This study suggested an alternative treatment possibility for SARS-CoV-2 infection. American Society for Microbiology 2022-03-09 /pmc/articles/PMC9006957/ /pubmed/35262371 http://dx.doi.org/10.1128/jvi.01705-21 Text en Copyright © 2022 American Society for Microbiology. https://doi.org/10.1128/ASMCopyrightv2All Rights Reserved (https://doi.org/10.1128/ASMCopyrightv2) . https://doi.org/10.1128/ASMCopyrightv2This article is made available via the PMC Open Access Subset for unrestricted noncommercial re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Pathogenesis and Immunity
Metz-Zumaran, Camila
Kee, Carmon
Doldan, Patricio
Guo, Cuncai
Stanifer, Megan L.
Boulant, Steeve
Increased Sensitivity of SARS-CoV-2 to Type III Interferon in Human Intestinal Epithelial Cells
title Increased Sensitivity of SARS-CoV-2 to Type III Interferon in Human Intestinal Epithelial Cells
title_full Increased Sensitivity of SARS-CoV-2 to Type III Interferon in Human Intestinal Epithelial Cells
title_fullStr Increased Sensitivity of SARS-CoV-2 to Type III Interferon in Human Intestinal Epithelial Cells
title_full_unstemmed Increased Sensitivity of SARS-CoV-2 to Type III Interferon in Human Intestinal Epithelial Cells
title_short Increased Sensitivity of SARS-CoV-2 to Type III Interferon in Human Intestinal Epithelial Cells
title_sort increased sensitivity of sars-cov-2 to type iii interferon in human intestinal epithelial cells
topic Pathogenesis and Immunity
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9006957/
https://www.ncbi.nlm.nih.gov/pubmed/35262371
http://dx.doi.org/10.1128/jvi.01705-21
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