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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...

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Autores principales: Kim, Kyumin, Calabrese, Peter, Wang, Shanshan, Qin, Chao, Rao, Youliang, Feng, Pinghui, Chen, Xiaojiang S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
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.
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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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