Parker, Matthew D; Stewart, Hazel; Shehata, Ola M; Lindsey, Benjamin B; Shah, Dhruv R; Hsu, Sharon; Keeley, Alexander J; Partridge, David G; Leary, Shay; Cope, Alison; +29 more... State, Amy; Johnson, Katie; Ali, Nasar; Raghei, Rasha; Heffer, Joe; Smith, Nikki; Zhang, Peijun; Gallis, Marta; Louka, Stavroula F; Hornsby, Hailey R; Alamri, Hatoon; Whiteley, Max; Foulkes, Benjamin H; Christou, Stella; Wolverson, Paige; Pohare, Manoj; Hansford, Samantha E; Green, Luke R; Evans, Cariad; Raza, Mohammad; Wang, Dennis; Firth, Andrew E; Edgar, James R; Gaudieri, Silvana; Mallal, Simon; COVID-19 Genomics UK (COG-UK) consortium; Collins, Mark O; Peden, Andrew A; de Silva, Thushan I; (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: https://doi.org/10.1038/s42003-022-03565-9
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Abstract
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.
Item Type | Article |
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Faculty and Department | Faculty of Infectious and Tropical Diseases > Dept of Clinical Research |
Research Centre | Covid-19 Research |
PubMed ID | 35790808 |
Elements ID | 181206 |