Altered subgenomic RNA abundance provides unique insight into SARS-CoV-2 B.1.1.7/Alpha variant infections.

Parker, Matthew DORCID logo; Stewart, HazelORCID logo; Shehata, Ola M; Lindsey, Benjamin BORCID logo; Shah, Dhruv RORCID logo; Hsu, Sharon; Keeley, Alexander JORCID logo; Partridge, David GORCID logo; Leary, Shay; Cope, Alison; +29 more...State, Amy; Johnson, Katie; Ali, Nasar; Raghei, Rasha; Heffer, JoeORCID logo; Smith, Nikki; Zhang, Peijun; Gallis, Marta; Louka, Stavroula FORCID logo; Hornsby, Hailey RORCID logo; Alamri, Hatoon; Whiteley, Max; Foulkes, Benjamin H; Christou, StellaORCID logo; Wolverson, PaigeORCID logo; Pohare, ManojORCID logo; Hansford, Samantha EORCID logo; Green, Luke RORCID logo; Evans, Cariad; Raza, Mohammad; Wang, DennisORCID logo; Firth, Andrew E; Edgar, James RORCID logo; Gaudieri, Silvana; Mallal, Simon; COVID-19 Genomics UK (COG-UK) consortium; Collins, Mark OORCID logo; Peden, Andrew AORCID logo; and de Silva, Thushan IORCID logo (2022) Altered subgenomic RNA abundance provides unique insight into SARS-CoV-2 B.1.1.7/Alpha variant infections. Communications biology, 5 (1). 666-. ISSN 2399-3642 DOI: 10.1038/s42003-022-03565-9
Copy

B.1.1.7 lineage SARS-CoV-2 is more transmissible, leads to greater clinical severity, and results in modest reductions in antibody neutralization. Subgenomic RNA (sgRNA) is produced by discontinuous transcription of the SARS-CoV-2 genome. Applying our tool (periscope) to ARTIC Network Oxford Nanopore Technologies genomic sequencing data from 4400 SARS-CoV-2 positive clinical samples, we show that normalised sgRNA is significantly increased in B.1.1.7 (alpha) infections (n = 879). This increase is seen over the previous dominant lineage in the UK, B.1.177 (n = 943), which is independent of genomic reads, E cycle threshold and days since symptom onset at sampling. A noncanonical sgRNA which could represent ORF9b is found in 98.4% of B.1.1.7 SARS-CoV-2 infections compared with only 13.8% of other lineages, with a 16-fold increase in median sgRNA abundance. We demonstrate that ORF9b protein levels are increased 6-fold in B.1.1.7 compared to a B lineage virus in vitro. We hypothesise that increased ORF9b in B.1.1.7 is a direct consequence of a triple nucleotide mutation in nucleocapsid (28280:GAT > CAT, D3L) creating a transcription regulatory-like sequence complementary to a region 3' of the genomic leader. These findings provide a unique insight into the biology of B.1.1.7 and support monitoring of sgRNA profiles to evaluate emerging potential variants of concern.


picture_as_pdf
s42003-022-03565-9.pdf
subject
Published Version
Available under Creative Commons: Attribution 4.0

View Download

Atom BibTeX OpenURL ContextObject in Span Multiline CSV OpenURL ContextObject Dublin Core Dublin Core MPEG-21 DIDL Data Cite XML EndNote HTML Citation JSON MARC (ASCII) MARC (ISO 2709) METS MODS RDF+N3 RDF+N-Triples RDF+XML RIOXX2 XML Reference Manager Refer Simple Metadata ASCII Citation EP3 XML
Export

Downloads