Altered subgenomic RNA abundance provides unique insight into SARS-CoV-2 B.1.1.7/Alpha variant infections.
Authors
Shehata, Ola M
Hsu, Sharon
Leary, Shay
Cope, Alison
State, Amy
Johnson, Katie
Ali, Nasar
Raghei, Rasha
Smith, Nikki
Zhang, Peijun
Gallis, Marta
Alamri, Hatoon
Whiteley, Max
Foulkes, Benjamin H
Evans, Cariad
Raza, Mohammad
Gaudieri, Silvana
Mallal, Simon
COVID-19 Genomics UK (COG-UK) consortium
Publication Date
2022-07-05Journal Title
Commun Biol
ISSN
2399-3642
Publisher
Springer Science and Business Media LLC
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Parker, M. D., Shaw, H., Shehata, O. M., Lindsey, B. B., Shah, D. R., Hsu, S., Keeley, A. J., et al. (2022). Altered subgenomic RNA abundance provides unique insight into SARS-CoV-2 B.1.1.7/Alpha variant infections.. Commun Biol https://doi.org/10.1038/s42003-022-03565-9
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.
Keywords
Article, /631/114, /631/326/596/4130, /45/23, /45/90, article
Sponsorship
Wellcome Trust (106207/Z/14/Z)
European Research Council (646891)
Identifiers
s42003-022-03565-9, 3565
External DOI: https://doi.org/10.1038/s42003-022-03565-9
This record's URL: https://www.repository.cam.ac.uk/handle/1810/338846
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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