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SARS-CoV-2 Omicron Induces Enhanced Mucosal Interferon Response Compared to other Variants of Concern, Associated with Restricted Replication in Human Lung Tissues
SARS-CoV-2 Omicron variant has been characterized by decreased clinical severity, raising the question of whether early variant-specific interactions within the mucosal surfaces of the respiratory tract could mediate its attenuated pathogenicity. Here, we employed ex vivo infection of native human n...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318963/ https://www.ncbi.nlm.nih.gov/pubmed/35891570 http://dx.doi.org/10.3390/v14071583 |
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author | Alfi, Or Hamdan, Marah Wald, Ori Yakirevitch, Arkadi Wandel, Ori Oiknine-Djian, Esther Gvili, Ben Knoller, Hadas Rozendorn, Noa Golan Berman, Hadar Adar, Sheera Vorontsov, Olesya Mandelboim, Michal Zakay-Rones, Zichria Oberbaum, Menachem Panet, Amos Wolf, Dana G. |
author_facet | Alfi, Or Hamdan, Marah Wald, Ori Yakirevitch, Arkadi Wandel, Ori Oiknine-Djian, Esther Gvili, Ben Knoller, Hadas Rozendorn, Noa Golan Berman, Hadar Adar, Sheera Vorontsov, Olesya Mandelboim, Michal Zakay-Rones, Zichria Oberbaum, Menachem Panet, Amos Wolf, Dana G. |
author_sort | Alfi, Or |
collection | PubMed |
description | SARS-CoV-2 Omicron variant has been characterized by decreased clinical severity, raising the question of whether early variant-specific interactions within the mucosal surfaces of the respiratory tract could mediate its attenuated pathogenicity. Here, we employed ex vivo infection of native human nasal and lung tissues to investigate the local-mucosal susceptibility and innate immune response to Omicron compared to Delta and earlier SARS-CoV-2 variants of concern (VOC). We show that the replication of Omicron in lung tissues is highly restricted compared to other VOC, whereas it remains relatively unchanged in nasal tissues. Mechanistically, Omicron induced a much stronger antiviral interferon response in infected tissues compared to Delta and earlier VOC-a difference, which was most striking in the lung tissues, where the innate immune response to all other SARS-CoV-2 VOC was blunted. Notably, blocking the innate immune signaling restored Omicron replication in the lung tissues. Our data provide new insights to the reduced lung involvement and clinical severity of Omicron. |
format | Online Article Text |
id | pubmed-9318963 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93189632022-07-27 SARS-CoV-2 Omicron Induces Enhanced Mucosal Interferon Response Compared to other Variants of Concern, Associated with Restricted Replication in Human Lung Tissues Alfi, Or Hamdan, Marah Wald, Ori Yakirevitch, Arkadi Wandel, Ori Oiknine-Djian, Esther Gvili, Ben Knoller, Hadas Rozendorn, Noa Golan Berman, Hadar Adar, Sheera Vorontsov, Olesya Mandelboim, Michal Zakay-Rones, Zichria Oberbaum, Menachem Panet, Amos Wolf, Dana G. Viruses Article SARS-CoV-2 Omicron variant has been characterized by decreased clinical severity, raising the question of whether early variant-specific interactions within the mucosal surfaces of the respiratory tract could mediate its attenuated pathogenicity. Here, we employed ex vivo infection of native human nasal and lung tissues to investigate the local-mucosal susceptibility and innate immune response to Omicron compared to Delta and earlier SARS-CoV-2 variants of concern (VOC). We show that the replication of Omicron in lung tissues is highly restricted compared to other VOC, whereas it remains relatively unchanged in nasal tissues. Mechanistically, Omicron induced a much stronger antiviral interferon response in infected tissues compared to Delta and earlier VOC-a difference, which was most striking in the lung tissues, where the innate immune response to all other SARS-CoV-2 VOC was blunted. Notably, blocking the innate immune signaling restored Omicron replication in the lung tissues. Our data provide new insights to the reduced lung involvement and clinical severity of Omicron. MDPI 2022-07-21 /pmc/articles/PMC9318963/ /pubmed/35891570 http://dx.doi.org/10.3390/v14071583 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Alfi, Or Hamdan, Marah Wald, Ori Yakirevitch, Arkadi Wandel, Ori Oiknine-Djian, Esther Gvili, Ben Knoller, Hadas Rozendorn, Noa Golan Berman, Hadar Adar, Sheera Vorontsov, Olesya Mandelboim, Michal Zakay-Rones, Zichria Oberbaum, Menachem Panet, Amos Wolf, Dana G. SARS-CoV-2 Omicron Induces Enhanced Mucosal Interferon Response Compared to other Variants of Concern, Associated with Restricted Replication in Human Lung Tissues |
title | SARS-CoV-2 Omicron Induces Enhanced Mucosal Interferon Response Compared to other Variants of Concern, Associated with Restricted Replication in Human Lung Tissues |
title_full | SARS-CoV-2 Omicron Induces Enhanced Mucosal Interferon Response Compared to other Variants of Concern, Associated with Restricted Replication in Human Lung Tissues |
title_fullStr | SARS-CoV-2 Omicron Induces Enhanced Mucosal Interferon Response Compared to other Variants of Concern, Associated with Restricted Replication in Human Lung Tissues |
title_full_unstemmed | SARS-CoV-2 Omicron Induces Enhanced Mucosal Interferon Response Compared to other Variants of Concern, Associated with Restricted Replication in Human Lung Tissues |
title_short | SARS-CoV-2 Omicron Induces Enhanced Mucosal Interferon Response Compared to other Variants of Concern, Associated with Restricted Replication in Human Lung Tissues |
title_sort | sars-cov-2 omicron induces enhanced mucosal interferon response compared to other variants of concern, associated with restricted replication in human lung tissues |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318963/ https://www.ncbi.nlm.nih.gov/pubmed/35891570 http://dx.doi.org/10.3390/v14071583 |
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