Role of spike in the pathogenic and antigenic behavior of SARS-CoV-2 BA.1 Omicron
The recently identified, globally predominant SARS-CoV-2 Omicron variant (BA.1) is highly transmissible, even in fully vaccinated individuals, and causes attenuated disease compared with other major viral variants recognized to date. The Omicron spike (S) protein, with an unusually large number of mutations, is considered the major driver of these phenotypes. We generated chimeric recombinant SARS-CoV-2 encoding the S gene of Omicron 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 escapes vaccine-induced humoral immunity, mainly due to mutations in the receptor binding motif (RBM), yet unlike naturally occurring Omicron, efficiently replicates in cell lines and primary-like distal lung cells. In K18-hACE2 mice, while Omicron causes mild, non-fatal infection, the Omicron S-carrying virus inflicts severe disease with a mortality rate of 80%. This indicates that while the vaccine escape of Omicron is defined by mutations in S, major determinants of viral pathogenicity reside outside of S.
| Errataetall: |
CommentIn: Nature. 2022 Nov;611(7934):17-18. - PMID 36271042 |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2023 |
|---|---|
| Enthalten in: |
bioRxiv : the preprint server for biology - (2023) vom: 10. Jan. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Chen, Da-Yuan [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Revised 20.01.2023 published: Electronic CommentIn: Nature. 2022 Nov;611(7934):17-18. - PMID 36271042 Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.1101/2022.10.13.512134 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM347777422 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM347777422 | ||
| 003 | DE-627 | ||
| 005 | 20231226034637.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2022.10.13.512134 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1159.xml |
| 035 | |a (DE-627)NLM347777422 | ||
| 035 | |a (NLM)36263066 | ||
| 035 | |a (PII)2022.10.13.512134 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Chen, Da-Yuan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Role of spike in the pathogenic and antigenic behavior of SARS-CoV-2 BA.1 Omicron |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 20.01.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a CommentIn: Nature. 2022 Nov;611(7934):17-18. - PMID 36271042 | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a The recently identified, globally predominant SARS-CoV-2 Omicron variant (BA.1) is highly transmissible, even in fully vaccinated individuals, and causes attenuated disease compared with other major viral variants recognized to date. The Omicron spike (S) protein, with an unusually large number of mutations, is considered the major driver of these phenotypes. We generated chimeric recombinant SARS-CoV-2 encoding the S gene of Omicron 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 escapes vaccine-induced humoral immunity, mainly due to mutations in the receptor binding motif (RBM), yet unlike naturally occurring Omicron, efficiently replicates in cell lines and primary-like distal lung cells. In K18-hACE2 mice, while Omicron causes mild, non-fatal infection, the Omicron S-carrying virus inflicts severe disease with a mortality rate of 80%. This indicates that while the vaccine escape of Omicron is defined by mutations in S, major determinants of viral pathogenicity reside outside of S | ||
| 650 | 4 | |a Preprint | |
| 700 | 1 | |a Kenney, Devin |e verfasserin |4 aut | |
| 700 | 1 | |a Chin, Chue-Vin |e verfasserin |4 aut | |
| 700 | 1 | |a Tavares, Alexander H |e verfasserin |4 aut | |
| 700 | 1 | |a Khan, Nazimuddin |e verfasserin |4 aut | |
| 700 | 1 | |a Conway, Hasahn L |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, GuanQun |e verfasserin |4 aut | |
| 700 | 1 | |a Choudhary, Manish C |e verfasserin |4 aut | |
| 700 | 1 | |a Gertje, Hans P |e verfasserin |4 aut | |
| 700 | 1 | |a O'Connell, Aoife K |e verfasserin |4 aut | |
| 700 | 1 | |a Kotton, Darrell N |e verfasserin |4 aut | |
| 700 | 1 | |a Herrmann, Alexandra |e verfasserin |4 aut | |
| 700 | 1 | |a Ensser, Armin |e verfasserin |4 aut | |
| 700 | 1 | |a Connor, John H |e verfasserin |4 aut | |
| 700 | 1 | |a Bosmann, Markus |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jonathan Z |e verfasserin |4 aut | |
| 700 | 1 | |a Gack, Michaela U |e verfasserin |4 aut | |
| 700 | 1 | |a Baker, Susan C |e verfasserin |4 aut | |
| 700 | 1 | |a Kirchdoerfer, Robert N |e verfasserin |4 aut | |
| 700 | 1 | |a Kataria, Yachana |e verfasserin |4 aut | |
| 700 | 1 | |a Crossland, Nicholas A |e verfasserin |4 aut | |
| 700 | 1 | |a Douam, Florian |e verfasserin |4 aut | |
| 700 | 1 | |a Saeed, Mohsan |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv : the preprint server for biology |d 2020 |g (2023) vom: 10. Jan. |w (DE-627)NLM31090014X |7 nnns |
| 773 | 1 | 8 | |g year:2023 |g day:10 |g month:01 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2022.10.13.512134 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2023 |b 10 |c 01 | ||