Rapid assembly of SARS-CoV-2 genomes reveals attenuation of the Omicron BA.1 variant through NSP6.

Autor: Taha TY; Gladstone Institutes, San Francisco, CA, USA. taha.taha@gladstone.ucsf.edu., Chen IP; Gladstone Institutes, San Francisco, CA, USA.; Department of Medicine, University of California, San Francisco, CA, USA., Hayashi JM; Gladstone Institutes, San Francisco, CA, USA., Tabata T; Gladstone Institutes, San Francisco, CA, USA., Walcott K; Gladstone Institutes, San Francisco, CA, USA., Kimmerly GR; Gladstone Institutes, San Francisco, CA, USA., Syed AM; Gladstone Institutes, San Francisco, CA, USA.; Innovative Genomics Institute, University of California, Berkeley, CA, USA., Ciling A; Gladstone Institutes, San Francisco, CA, USA.; Innovative Genomics Institute, University of California, Berkeley, CA, USA., Suryawanshi RK; Gladstone Institutes, San Francisco, CA, USA., Martin HS; Gladstone Institutes, San Francisco, CA, USA.; Department of Chemistry, University of California, Berkeley, CA, USA., Bach BH; Innovative Genomics Institute, University of California, Berkeley, CA, USA., Tsou CL; Gladstone Institutes, San Francisco, CA, USA., Montano M; Gladstone Institutes, San Francisco, CA, USA., Khalid MM; Gladstone Institutes, San Francisco, CA, USA., Sreekumar BK; Gladstone Institutes, San Francisco, CA, USA., Renuka Kumar G; Gladstone Institutes, San Francisco, CA, USA., Wyman S; Innovative Genomics Institute, University of California, Berkeley, CA, USA., Doudna JA; Gladstone Institutes, San Francisco, CA, USA.; Innovative Genomics Institute, University of California, Berkeley, CA, USA.; Department of Chemistry, University of California, Berkeley, CA, USA.; Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.; Howard Hughes Medical Institute, University of California, Berkeley, CA, USA.; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, CA, USA., Ott M; Gladstone Institutes, San Francisco, CA, USA. melanie.ott@gladstone.ucsf.edu.; Department of Medicine, University of California, San Francisco, CA, USA. melanie.ott@gladstone.ucsf.edu.; Chan Zuckerberg Biohub - San Francisco, San Francisco, CA, USA. melanie.ott@gladstone.ucsf.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Apr 21; Vol. 14 (1), pp. 2308. Date of Electronic Publication: 2023 Apr 21.
DOI: 10.1038/s41467-023-37787-0
Abstrakt: Although the SARS-CoV-2 Omicron variant (BA.1) spread rapidly across the world and effectively evaded immune responses, its viral fitness in cell and animal models was reduced. The precise nature of this attenuation remains unknown as generating replication-competent viral genomes is challenging because of the length of the viral genome (~30 kb). Here, we present a plasmid-based viral genome assembly and rescue strategy (pGLUE) that constructs complete infectious viruses or noninfectious subgenomic replicons in a single ligation reaction with >80% efficiency. Fully sequenced replicons and infectious viral stocks can be generated in 1 and 3 weeks, respectively. By testing a series of naturally occurring viruses as well as Delta-Omicron chimeric replicons, we show that Omicron nonstructural protein 6 harbors critical attenuating mutations, which dampen viral RNA replication and reduce lipid droplet consumption. Thus, pGLUE overcomes remaining barriers to broadly study SARS-CoV-2 replication and reveals deficits in nonstructural protein function underlying Omicron attenuation.
(© 2023. The Author(s).)
Databáze: MEDLINE
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