The roles of APOBEC-mediated RNA editing in SARS-CoV-2 mutations, replication and fitness
Abstract 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 to...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-19067-x |
| _version_ | 1811267488043761664 |
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| author | Kyumin Kim Peter Calabrese Shanshan Wang Chao Qin Youliang Rao Pinghui Feng Xiaojiang S. Chen |
| author_facet | Kyumin Kim Peter Calabrese Shanshan Wang Chao Qin Youliang Rao Pinghui Feng Xiaojiang S. Chen |
| author_sort | Kyumin Kim |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-12T21:03:27Z |
| format | Article |
| id | doaj.art-2b791fb837ed48089c51d4e1c3b1fed6 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T21:03:27Z |
| publishDate | 2022-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-2b791fb837ed48089c51d4e1c3b1fed62022-12-22T03:16:47ZengNature PortfolioScientific Reports2045-23222022-09-0112111510.1038/s41598-022-19067-xThe roles of APOBEC-mediated RNA editing in SARS-CoV-2 mutations, replication and fitnessKyumin Kim0Peter Calabrese1Shanshan Wang2Chao Qin3Youliang Rao4Pinghui Feng5Xiaojiang S. Chen6Molecular and Computational Biology Section, University of Southern CaliforniaQuantitative and Computational Biology Department, University of Southern CaliforniaMolecular and Computational Biology Section, University of Southern CaliforniaSection of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern CaliforniaSection of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern CaliforniaSection of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern CaliforniaMolecular and Computational Biology Section, University of Southern CaliforniaAbstract 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.https://doi.org/10.1038/s41598-022-19067-x |
| spellingShingle | Kyumin Kim Peter Calabrese Shanshan Wang Chao Qin Youliang Rao Pinghui Feng Xiaojiang S. Chen The roles of APOBEC-mediated RNA editing in SARS-CoV-2 mutations, replication and fitness Scientific Reports |
| 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 |
| url | https://doi.org/10.1038/s41598-022-19067-x |
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