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Spike and nsp6 are key determinants of SARS-CoV-2 Omicron BA.1 attenuation.
Chen, Da-Yuan; Chin, Chue Vin; Kenney, Devin; Tavares, Alexander H; Khan, Nazimuddin; Conway, Hasahn L; Liu, GuanQun; Choudhary, Manish C; Gertje, Hans P; O'Connell, Aoife K; Adams, Scott; Kotton, Darrell N; Herrmann, Alexandra; Ensser, Armin; Connor, John H; Bosmann, Markus; Li, Jonathan Z; Gack, Michaela U; Baker, Susan C; Kirchdoerfer, Robert N; Kataria, Yachana; Crossland, Nicholas A; Douam, Florian; Saeed, Mohsan.
  • Chen DY; Department of Biochemistry, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.
  • Chin CV; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
  • Kenney D; Department of Biochemistry, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.
  • Tavares AH; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
  • Khan N; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
  • Conway HL; Department of Microbiology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.
  • Liu G; Department of Biochemistry, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.
  • Choudhary MC; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
  • Gertje HP; Department of Biochemistry, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.
  • O'Connell AK; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
  • Adams S; Department of Biochemistry, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.
  • Kotton DN; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
  • Herrmann A; Florida Research and Innovation Center, Cleveland Clinic, Port St. Lucie, FL, USA.
  • Ensser A; Brigham and Women's Hospital, Boston, MA, USA.
  • Connor JH; Harvard Medical School, Cambridge, MA, USA.
  • Bosmann M; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
  • Li JZ; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
  • Gack MU; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
  • Baker SC; Department of Microbiology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.
  • Kirchdoerfer RN; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA, USA.
  • Kataria Y; The Pulmonary Center and Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.
  • Crossland NA; Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
  • Douam F; Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
  • Saeed M; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
Nature ; 615(7950): 143-150, 2023 03.
Статья в английский | MEDLINE | ID: covidwho-2185940
ABSTRACT
The SARS-CoV-2 Omicron variant is more immune evasive and less virulent than other major viral variants that have so far been recognized1-12. 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.
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Полный текст: Имеется в наличии Коллекция: Международные базы данных база данных: MEDLINE Основная тема: Virulence / Virulence Factors / Spike Glycoprotein, Coronavirus / Coronavirus Nucleocapsid Proteins / SARS-CoV-2 / COVID-19 Темы: Вакцина / Варианты Пределы темы: Животные / Люди Язык: английский Журнал: Nature Год: 2023 Тип: Статья Аффилированная страна: S41586-023-05697-2

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Полный текст: Имеется в наличии Коллекция: Международные базы данных база данных: MEDLINE Основная тема: Virulence / Virulence Factors / Spike Glycoprotein, Coronavirus / Coronavirus Nucleocapsid Proteins / SARS-CoV-2 / COVID-19 Темы: Вакцина / Варианты Пределы темы: Животные / Люди Язык: английский Журнал: Nature Год: 2023 Тип: Статья Аффилированная страна: S41586-023-05697-2