Journal article
Altered subgenomic RNA abundance provides unique insight into SARS-CoV-2 B.1.1.7/Alpha variant infections
Communications Biology, Vol.5(1), Art. 666
2022
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.
Details
- Title
- Altered subgenomic RNA abundance provides unique insight into SARS-CoV-2 B.1.1.7/Alpha variant infections
- Authors/Creators
- M.D. Parker (Author/Creator)H. Stewart (Author/Creator)O.M. Shehata (Author/Creator)B.B. Lindsey (Author/Creator)D.R. Shah (Author/Creator)S. Hsu (Author/Creator)A.J. Keeley (Author/Creator)D.G. Partridge (Author/Creator)S. Leary (Author/Creator)A. Cope (Author/Creator)A. State (Author/Creator)K. Johnson (Author/Creator)N. Ali (Author/Creator)R. Raghei (Author/Creator)J. Heffer (Author/Creator)N. Smith (Author/Creator)P. Zhang (Author/Creator)M. Gallis (Author/Creator)S.F. Louka (Author/Creator)H.R. Hornsby (Author/Creator)H. Alamri (Author/Creator)M. Whiteley (Author/Creator)B.H. Foulkes (Author/Creator)S. Christou (Author/Creator)P. Wolverson (Author/Creator)M. Pohare (Author/Creator)S.E. Hansford (Author/Creator)L.R. Green (Author/Creator)C. Evans (Author/Creator)M. Raza (Author/Creator)D. Wang (Author/Creator)A.E. Firth (Author/Creator)J.R. Edgar (Author/Creator)S. Gaudieri (Author/Creator)S. Mallal (Author/Creator)M.O. Collins (Author/Creator)A.A. Peden (Author/Creator)T.I. de Silva (Author/Creator)
- Publication Details
- Communications Biology, Vol.5(1), Art. 666
- Publisher
- Nature Research
- Identifiers
- 991005545151407891
- Copyright
- © 2022 The Authors.
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Citation topics
- 1 Clinical & Life Sciences
- 1.104 Virology - General
- 1.104.1353 Coronavirus Research
- Web Of Science research areas
- Biology
- ESI research areas
- Biology & Biochemistry