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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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