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Altered subgenomic RNA abundance provides unique insight into SARS-CoV-2 B.1.1.7/Alpha variant infections
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 Nanopor...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255483/ https://www.ncbi.nlm.nih.gov/pubmed/35790808 http://dx.doi.org/10.1038/s42003-022-03565-9 |
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author | 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 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 Collins, Mark O. Peden, Andrew A. de Silva, Thushan I. |
author_facet | 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 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 Collins, Mark O. Peden, Andrew A. de Silva, Thushan I. |
author_sort | Parker, Matthew D. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9255483 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-92554832022-07-06 Altered subgenomic RNA abundance provides unique insight into SARS-CoV-2 B.1.1.7/Alpha variant infections 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 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 Collins, Mark O. Peden, Andrew A. de Silva, Thushan I. Commun Biol Article 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. Nature Publishing Group UK 2022-07-05 /pmc/articles/PMC9255483/ /pubmed/35790808 http://dx.doi.org/10.1038/s42003-022-03565-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article 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 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 Collins, Mark O. Peden, Andrew A. de Silva, Thushan I. Altered subgenomic RNA abundance provides unique insight into SARS-CoV-2 B.1.1.7/Alpha variant infections |
title | Altered subgenomic RNA abundance provides unique insight into SARS-CoV-2 B.1.1.7/Alpha variant infections |
title_full | Altered subgenomic RNA abundance provides unique insight into SARS-CoV-2 B.1.1.7/Alpha variant infections |
title_fullStr | Altered subgenomic RNA abundance provides unique insight into SARS-CoV-2 B.1.1.7/Alpha variant infections |
title_full_unstemmed | Altered subgenomic RNA abundance provides unique insight into SARS-CoV-2 B.1.1.7/Alpha variant infections |
title_short | Altered subgenomic RNA abundance provides unique insight into SARS-CoV-2 B.1.1.7/Alpha variant infections |
title_sort | altered subgenomic rna abundance provides unique insight into sars-cov-2 b.1.1.7/alpha variant infections |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255483/ https://www.ncbi.nlm.nih.gov/pubmed/35790808 http://dx.doi.org/10.1038/s42003-022-03565-9 |
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