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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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Detalles Bibliográficos
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
Descripción
Sumario: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.