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http://purl.uniprot.org/citations/36207334http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/36207334http://www.w3.org/2000/01/rdf-schema#comment"Variant of concern (VOC) Omicron-BA.1 has achieved global predominance in early 2022. Therefore, surveillance and comprehensive characterization of Omicron-BA.1 in advanced primary cell culture systems and animal models are urgently needed. Here, we characterize Omicron-BA.1 and recombinant Omicron-BA.1 spike gene mutants in comparison with VOC Delta in well-differentiated primary human nasal and bronchial epithelial cells in vitro, followed by in vivo fitness characterization in hamsters, ferrets and hACE2-expressing mice, and immunized hACE2-mice. We demonstrate a spike-mediated enhancement of early replication of Omicron-BA.1 in nasal epithelial cultures, but limited replication in bronchial epithelial cultures. In hamsters, Delta shows dominance over Omicron-BA.1, and in ferrets Omicron-BA.1 infection is abortive. In hACE2-knock-in mice, Delta and a Delta spike clone also show dominance over Omicron-BA.1 and an Omicron-BA.1 spike clone, respectively. Interestingly, in naïve K18-hACE2 mice, we observe Delta spike-mediated increased replication and pathogenicity and Omicron-BA.1 spike-mediated reduced replication and pathogenicity, suggesting that the spike gene is a major determinant of replication and pathogenicity. Finally, the Omicron-BA.1 spike clone is less well-controlled by mRNA-vaccination in K18-hACE2-mice and becomes more competitive compared to the progenitor and Delta spike clones, suggesting that spike gene-mediated immune evasion is another important factor that led to Omicron-BA.1 dominance."xsd:string
http://purl.uniprot.org/citations/36207334http://purl.org/dc/terms/identifier"doi:10.1038/s41467-022-33632-y"xsd:string
http://purl.uniprot.org/citations/36207334http://purl.uniprot.org/core/author"Hoffmann B."xsd:string
http://purl.uniprot.org/citations/36207334http://purl.uniprot.org/core/author"Thiel V."xsd:string
http://purl.uniprot.org/citations/36207334http://purl.uniprot.org/core/author"Beer M."xsd:string
http://purl.uniprot.org/citations/36207334http://purl.uniprot.org/core/author"Hoper D."xsd:string
http://purl.uniprot.org/citations/36207334http://purl.uniprot.org/core/author"Steiner S."xsd:string
http://purl.uniprot.org/citations/36207334http://purl.uniprot.org/core/author"Hoffmann D."xsd:string
http://purl.uniprot.org/citations/36207334http://purl.uniprot.org/core/author"Breithaupt A."xsd:string
http://purl.uniprot.org/citations/36207334http://purl.uniprot.org/core/author"Wernike K."xsd:string
http://purl.uniprot.org/citations/36207334http://purl.uniprot.org/core/author"Rauch A."xsd:string
http://purl.uniprot.org/citations/36207334http://purl.uniprot.org/core/author"Dijkman R."xsd:string
http://purl.uniprot.org/citations/36207334http://purl.uniprot.org/core/author"Ebert N."xsd:string
http://purl.uniprot.org/citations/36207334http://purl.uniprot.org/core/author"Ciesek S."xsd:string
http://purl.uniprot.org/citations/36207334http://purl.uniprot.org/core/author"Stalder H."xsd:string
http://purl.uniprot.org/citations/36207334http://purl.uniprot.org/core/author"Widera M."xsd:string
http://purl.uniprot.org/citations/36207334http://purl.uniprot.org/core/author"Benarafa C."xsd:string
http://purl.uniprot.org/citations/36207334http://purl.uniprot.org/core/author"Halwe N.J."xsd:string
http://purl.uniprot.org/citations/36207334http://purl.uniprot.org/core/author"Kelly J.N."xsd:string
http://purl.uniprot.org/citations/36207334http://purl.uniprot.org/core/author"Taddeo A."xsd:string
http://purl.uniprot.org/citations/36207334http://purl.uniprot.org/core/author"Thomann L."xsd:string
http://purl.uniprot.org/citations/36207334http://purl.uniprot.org/core/author"Ulrich L."xsd:string
http://purl.uniprot.org/citations/36207334http://purl.uniprot.org/core/author"Marti T.M."xsd:string
http://purl.uniprot.org/citations/36207334http://purl.uniprot.org/core/author"Schmied K."xsd:string