Spike and nsp6 are key determinants of SARS-CoV-2 Omicron BA.1 attenuation.

Autor: Chen DY; Department of Biochemistry, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA., Chin CV; Department of Biochemistry, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA., Kenney D; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.; Department of Microbiology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA., Tavares AH; Department of Biochemistry, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA., Khan N; Department of Biochemistry, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA., Conway HL; Department of Biochemistry, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA., Liu G; Florida Research and Innovation Center, Cleveland Clinic, Port St. Lucie, FL, USA., Choudhary MC; Brigham and Women's Hospital, Boston, MA, USA.; Harvard Medical School, Cambridge, MA, USA., Gertje HP; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA., O'Connell AK; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA., Adams S; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.; Department of Microbiology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA., Kotton DN; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA, USA.; The Pulmonary Center and Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA., Herrmann A; Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany., Ensser A; Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany., Connor JH; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.; Department of Microbiology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA., Bosmann M; The Pulmonary Center and Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.; Department of Pathology and Laboratory Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.; Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany., Li JZ; Brigham and Women's Hospital, Boston, MA, USA.; Harvard Medical School, Cambridge, MA, USA., Gack MU; Florida Research and Innovation Center, Cleveland Clinic, Port St. Lucie, FL, USA., Baker SC; Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA.; Infectious Disease and Immunology Research Institute, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA., Kirchdoerfer RN; Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin-Madison, Madison, WI, USA., Kataria Y; Department of Pathology and Laboratory Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA., Crossland NA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.; Department of Pathology and Laboratory Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA., Douam F; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.; Department of Microbiology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA., Saeed M; Department of Biochemistry, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA. msaeed1@bu.edu.; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA. msaeed1@bu.edu.
Jazyk: angličtina
Zdroj: Nature [Nature] 2023 Mar; Vol. 615 (7950), pp. 143-150. Date of Electronic Publication: 2023 Jan 11.
DOI: 10.1038/s41586-023-05697-2
Abstrakt: The SARS-CoV-2 Omicron variant is more immune evasive and less virulent than other major viral variants that have so far been recognized 1-12 . The Omicron spike (S) protein, which has an unusually large number of mutations, is considered to be the main driver of these phenotypes. Here we generated chimeric recombinant SARS-CoV-2 encoding the S gene of Omicron (BA.1 lineage) in the backbone of an ancestral SARS-CoV-2 isolate, and compared this virus with the naturally circulating Omicron variant. The Omicron S-bearing virus robustly escaped vaccine-induced humoral immunity, mainly owing to mutations in the receptor-binding motif; however, unlike naturally occurring Omicron, it efficiently replicated in cell lines and primary-like distal lung cells. Similarly, in K18-hACE2 mice, although virus bearing Omicron S caused less severe disease than the ancestral virus, its virulence was not attenuated to the level of Omicron. Further investigation showed that mutating non-structural protein 6 (nsp6) in addition to the S protein was sufficient to recapitulate the attenuated phenotype of Omicron. This indicates that although the vaccine escape of Omicron is driven by mutations in S, the pathogenicity of Omicron is determined by mutations both in and outside of the S protein.
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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