The spike gene is a major determinant for the SARS-CoV-2 Omicron-BA.1 phenotype.

Barut, G Tuba; Halwe, Nico Joel; Taddeo, Adriano; Kelly, Jenna N; Schön, Jacob; Ebert, Nadine; Ulrich, Lorenz; Devisme, Christelle; Steiner, Silvio; Trüeb, Bettina Salome; Hoffmann, Bernd; Berenguer Veiga, Inês; Leborgne, Nathan Georges François; Aguiar Moreira, Etori; Breithaupt, Angele; Wylezich, Claudia; Höper, Dirk; Wernike, Kerstin; Godel, Aurélie; Thomann, Lisa; ... (2022). The spike gene is a major determinant for the SARS-CoV-2 Omicron-BA.1 phenotype. Nature Communications, 13(1), p. 5929. Springer Nature 10.1038/s41467-022-33632-y

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Infectiology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Pneumologie (Erwachsene)
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Thoraxchirurgie
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Thoracic Surgery
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Veterinary Bacteriology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Barut, Güliz Tuba; Taddeo, Adriano; Kelly, Jenna Nicole; Ebert, Nadine; Devisme, Christelle; Steiner, Silvio; Trüeb, Bettina Salome; Berenguer Veiga, Inês Margarida; Leborgne, Nathan Georges François; Aguiar Moreira, Etori; Godel, Aurélie; Thomann, Lisa Jane; Flück, Vera; Stalder, Hanspeter; Brügger, Melanie; Oliveira Esteves Criblez, Blandina Isabel; Beilleau, Guillaume Francois Frederic; Kratzel, Annika; Schmied, Kimberly Shadia; Ochsenbein, Sarah; Lang, Reto Mario; Machahua Huamani, Carlos Esteban; Dorn, Patrick; Marti, Thomas; Funke-Chambour, Manuela; Rauch, Andri; Dijkman, Ronald; Alves, Marco; Benarafa, Charaf and Thiel, Volker Earl

Subjects:

600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2041-1723

Publisher:

Springer Nature

Language:

English

Submitter:

Pubmed Import

Date Deposited:

10 Oct 2022 14:53

Last Modified:

05 Dec 2022 16:26

Publisher DOI:

10.1038/s41467-022-33632-y

PubMed ID:

36207334

BORIS DOI:

10.48350/173612

URI:

https://boris.unibe.ch/id/eprint/173612

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