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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

Authors :
Or Alfi
Marah Hamdan
Ori Wald
Arkadi Yakirevitch
Ori Wandel
Esther Oiknine-Djian
Ben Gvili
Hadas Knoller
Noa Rozendorn
Hadar Golan Berman
Sheera Adar
Olesya Vorontsov
Michal Mandelboim
Zichria Zakay-Rones
Menachem Oberbaum
Amos Panet
Dana G. Wolf
Source :
Viruses, Vol 14, Iss 7, p 1583 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

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.

Details

Language :
English
ISSN :
19994915
Volume :
14
Issue :
7
Database :
Directory of Open Access Journals
Journal :
Viruses
Publication Type :
Academic Journal
Accession number :
edsdoj.62d62748db8a476396f1557eae6378af
Document Type :
article
Full Text :
https://doi.org/10.3390/v14071583