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The roles of APOBEC-mediated RNA editing in SARS-CoV-2 mutations, replication and fitness
During COVID-19 pandemic, mutations of SARS-CoV-2 produce new strains that can be more infectious or evade vaccines. Viral RNA mutations can arise from misincorporation by RNA-polymerases and modification by host factors. Analysis of SARS-CoV-2 sequence from patients showed a strong bias toward C-to...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9470679/ https://www.ncbi.nlm.nih.gov/pubmed/36100631 http://dx.doi.org/10.1038/s41598-022-19067-x |
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author | Kim, Kyumin Calabrese, Peter Wang, Shanshan Qin, Chao Rao, Youliang Feng, Pinghui Chen, Xiaojiang S. |
author_facet | Kim, Kyumin Calabrese, Peter Wang, Shanshan Qin, Chao Rao, Youliang Feng, Pinghui Chen, Xiaojiang S. |
author_sort | Kim, Kyumin |
collection | PubMed |
description | During COVID-19 pandemic, mutations of SARS-CoV-2 produce new strains that can be more infectious or evade vaccines. Viral RNA mutations can arise from misincorporation by RNA-polymerases and modification by host factors. Analysis of SARS-CoV-2 sequence from patients showed a strong bias toward C-to-U mutation, suggesting a potential mutational role by host APOBEC cytosine deaminases that possess broad anti-viral activity. We report the first experimental evidence demonstrating that APOBEC3A, APOBEC1, and APOBEC3G can edit on specific sites of SARS-CoV-2 RNA to produce C-to-U mutations. However, SARS-CoV-2 replication and viral progeny production in Caco-2 cells are not inhibited by the expression of these APOBECs. Instead, expression of wild-type APOBEC3 greatly promotes viral replication/propagation, suggesting that SARS-CoV-2 utilizes the APOBEC-mediated mutations for fitness and evolution. Unlike the random mutations, this study suggests the predictability of all possible viral genome mutations by these APOBECs based on the UC/AC motifs and the viral genomic RNA structure. |
format | Online Article Text |
id | pubmed-9470679 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-94706792022-09-15 The roles of APOBEC-mediated RNA editing in SARS-CoV-2 mutations, replication and fitness Kim, Kyumin Calabrese, Peter Wang, Shanshan Qin, Chao Rao, Youliang Feng, Pinghui Chen, Xiaojiang S. Sci Rep Article During COVID-19 pandemic, mutations of SARS-CoV-2 produce new strains that can be more infectious or evade vaccines. Viral RNA mutations can arise from misincorporation by RNA-polymerases and modification by host factors. Analysis of SARS-CoV-2 sequence from patients showed a strong bias toward C-to-U mutation, suggesting a potential mutational role by host APOBEC cytosine deaminases that possess broad anti-viral activity. We report the first experimental evidence demonstrating that APOBEC3A, APOBEC1, and APOBEC3G can edit on specific sites of SARS-CoV-2 RNA to produce C-to-U mutations. However, SARS-CoV-2 replication and viral progeny production in Caco-2 cells are not inhibited by the expression of these APOBECs. Instead, expression of wild-type APOBEC3 greatly promotes viral replication/propagation, suggesting that SARS-CoV-2 utilizes the APOBEC-mediated mutations for fitness and evolution. Unlike the random mutations, this study suggests the predictability of all possible viral genome mutations by these APOBECs based on the UC/AC motifs and the viral genomic RNA structure. Nature Publishing Group UK 2022-09-13 /pmc/articles/PMC9470679/ /pubmed/36100631 http://dx.doi.org/10.1038/s41598-022-19067-x 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Kim, Kyumin Calabrese, Peter Wang, Shanshan Qin, Chao Rao, Youliang Feng, Pinghui Chen, Xiaojiang S. The roles of APOBEC-mediated RNA editing in SARS-CoV-2 mutations, replication and fitness |
title | The roles of APOBEC-mediated RNA editing in SARS-CoV-2 mutations, replication and fitness |
title_full | The roles of APOBEC-mediated RNA editing in SARS-CoV-2 mutations, replication and fitness |
title_fullStr | The roles of APOBEC-mediated RNA editing in SARS-CoV-2 mutations, replication and fitness |
title_full_unstemmed | The roles of APOBEC-mediated RNA editing in SARS-CoV-2 mutations, replication and fitness |
title_short | The roles of APOBEC-mediated RNA editing in SARS-CoV-2 mutations, replication and fitness |
title_sort | roles of apobec-mediated rna editing in sars-cov-2 mutations, replication and fitness |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9470679/ https://www.ncbi.nlm.nih.gov/pubmed/36100631 http://dx.doi.org/10.1038/s41598-022-19067-x |
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