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

Matthew D Parker ORCID logo; Hazel Stewart ORCID logo; Ola M Shehata; Benjamin B Lindsey ORCID logo; Dhruv R Shah ORCID logo; Sharon Hsu; Alexander J Keeley ORCID logo; David G Partridge ORCID logo; Shay Leary; Alison Cope; +29 more... Amy State; Katie Johnson; Nasar Ali; Rasha Raghei; Joe Heffer ORCID logo; Nikki Smith; Peijun Zhang; Marta Gallis; Stavroula F Louka ORCID logo; Hailey R Hornsby ORCID logo; Hatoon Alamri; Max Whiteley; Benjamin H Foulkes; Stella Christou ORCID logo; Paige Wolverson ORCID logo; Manoj Pohare ORCID logo; Samantha E Hansford ORCID logo; Luke R Green ORCID logo; Cariad Evans; Mohammad Raza; Dennis Wang ORCID logo; Andrew E Firth; James R Edgar ORCID logo; Silvana Gaudieri; Simon Mallal; COVID-19 Genomics UK (COG-UK) consortium; Mark O Collins ORCID logo; Andrew A Peden ORCID logo; Thushan I de Silva ORCID 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: 4.0

View Download

Atom BibTeX OpenURL ContextObject in Span Multiline CSV OpenURL ContextObject Dublin Core Dublin Core MPEG-21 DIDL 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