RT Journal Article
SR Electronic
T1 Altered Subgenomic RNA Expression in SARS-CoV-2 B.1.1.7 Infections
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.03.02.433156
DO 10.1101/2021.03.02.433156
A1 Matthew D Parker
A1 Benjamin B. Lindsey
A1 Dhruv R Shah
A1 Sharon Hsu
A1 Alexander J Keeley
A1 David G Partridge
A1 Shay Leary
A1 Alison Cope
A1 Amy State
A1 Katie Johnson
A1 Nasar Ali
A1 Rasha Raghei
A1 Joe Heffer
A1 Nikki Smith
A1 Peijun Zhang
A1 Marta Gallis
A1 Stavroula F Louka
A1 Hailey R Hornsby
A1 Max Whiteley
A1 Benjamin H Foulkes
A1 Stella Christou
A1 Paige Wolverson
A1 Manoj Pohare
A1 Samantha E Hansford
A1 Luke R Green
A1 Cariad Evans
A1 Mohammad Raza
A1 Dennis Wang
A1 Silvana Gaudieri
A1 Simon Mallal
A1 The COVID-19 Genomics UK (COG-UK) consortium
A1 Thushan I. de Silva
YR 2021
UL http://biorxiv.org/content/early/2021/03/04/2021.03.02.433156.abstract
AB SARS-CoV-2 lineage B.1.1.7 viruses are more transmissible, may lead to greater clinical severity, and result in modest reductions in antibody neutralization. subgenomic RNA (sgRNA) is produced by discontinuous transcription of the SARS-CoV-2 genome and is a crucial step in the SARS-CoV-2 life cycle. Applying our tool (periscope) to ARTIC Network Oxford Nanopore genomic sequencing data from 4400 SARS-CoV-2 positive clinical samples, we show that normalised sgRNA expression profiles are significantly increased in B.1.1.7 infections (n=879). This increase is seen over the previous dominant circulating lineage in the UK, B.1.177 (n=943), which is independent of genomic reads, E gene 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 expression. We hypothesise that this 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 in sequence data to evaluate emerging potential variants of concern.One Sentence Summary The recently emerged and more transmissible SARS-CoV-2 lineage B.1.1.7 shows greater subgenomic RNA expression in clinical infections and enhanced expression of a noncanonical subgenomic RNA near ORF9b.Competing Interest StatementThe authors have declared no competing interest.