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

التفاصيل البيبلوغرافية
العنوان: Rapid assembly of SARS-CoV-2 genomes reveals attenuation of the Omicron BA.1 variant through NSP6.
المؤلفون: Taha TY, Chen IP, Hayashi JM, Tabata T, Walcott K, Kimmerly GR, Syed AM, Ciling A, Suryawanshi RK, Martin HS, Bach BH, Tsou CL, Montano M, Khalid MM, Sreekumar BK, Kumar GR, Wyman S, Doudna JA, Ott M
المصدر: BioRxiv : the preprint server for biology [bioRxiv] 2023 Feb 09. Date of Electronic Publication: 2023 Feb 09.
نوع المنشور: Preprint
اللغة: English
بيانات الدورية: Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE
مستخلص: 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 (30kb). Here, we designed a plasmid-based viral genome assembly and resc ue 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.
التعليقات: Update in: Nat Commun. 2023 Apr 21;14(1):2308. (PMID: 37085489)
تواريخ الأحداث: Date Created: 20230217 Latest Revision: 20230513
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC9934579
DOI: 10.1101/2023.01.31.525914
PMID: 36798416
قاعدة البيانات: MEDLINE
الوصف
DOI:10.1101/2023.01.31.525914