APOBEC3F Is a Mutational Driver of the Human Monkeypox Virus Identified in the 2022 Outbreak
© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com..
BACKGROUND: On May 6, 2022, a powerful outbreak of monkeypox virus (MPXV) had been reported outside of Africa, with many continuing new cases being reported around the world. Analysis of mutations among the 2 different lineages present in the 2021 and 2022 outbreaks revealed the presence of G->A mutations occurring in the 5'GpA context, indicative of APOBEC3 cytidine deaminase activity.
METHODS: By using a sensitive polymerase chain reaction (differential DNA denaturation PCR) method allowing differential amplification of AT-rich DNA, we analyzed the level of APOBEC3-induced MPXV editing in infected cells and in patients.
RESULTS: We demonstrate that G->A hypermutated MPXV genomes can be recovered experimentally from APOBEC3 transfection followed by MPXV infection. Here, among the 7 human APOBEC3 cytidine deaminases (A3A-A3C, A3DE, A3F-A3H), only APOBEC3F was capable of extensively deaminating cytidine residues in MPXV genomes. Hyperedited genomes were also recovered in ∼42% of analyzed patients. Moreover, we demonstrate that substantial repair of these mutations occurs. Upon selection, corrected G->A mutations escaping drift loss contribute to the MPXV evolution observed in the current epidemic.
CONCLUSIONS: Stochastic or transient overexpression of the APOBEC3F gene exposes the MPXV genome to a broad spectrum of mutations that may be modeling the mutational landscape after multiple cycles of viral replication.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:228 |
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| Enthalten in: |
The Journal of infectious diseases - 228(2023), 10 vom: 11. Nov., Seite 1421-1429 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Suspène, Rodolphe [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.11.2023 Date Revised 25.04.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/infdis/jiad165 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM357270142 |
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| 500 | |a Date Revised 25.04.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com. | ||
| 520 | |a BACKGROUND: On May 6, 2022, a powerful outbreak of monkeypox virus (MPXV) had been reported outside of Africa, with many continuing new cases being reported around the world. Analysis of mutations among the 2 different lineages present in the 2021 and 2022 outbreaks revealed the presence of G->A mutations occurring in the 5'GpA context, indicative of APOBEC3 cytidine deaminase activity | ||
| 520 | |a METHODS: By using a sensitive polymerase chain reaction (differential DNA denaturation PCR) method allowing differential amplification of AT-rich DNA, we analyzed the level of APOBEC3-induced MPXV editing in infected cells and in patients | ||
| 520 | |a RESULTS: We demonstrate that G->A hypermutated MPXV genomes can be recovered experimentally from APOBEC3 transfection followed by MPXV infection. Here, among the 7 human APOBEC3 cytidine deaminases (A3A-A3C, A3DE, A3F-A3H), only APOBEC3F was capable of extensively deaminating cytidine residues in MPXV genomes. Hyperedited genomes were also recovered in ∼42% of analyzed patients. Moreover, we demonstrate that substantial repair of these mutations occurs. Upon selection, corrected G->A mutations escaping drift loss contribute to the MPXV evolution observed in the current epidemic | ||
| 520 | |a CONCLUSIONS: Stochastic or transient overexpression of the APOBEC3F gene exposes the MPXV genome to a broad spectrum of mutations that may be modeling the mutational landscape after multiple cycles of viral replication | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a APOBEC3F | |
| 650 | 4 | |a cytidine deaminase | |
| 650 | 4 | |a monkeypox virus | |
| 650 | 4 | |a outbreak | |
| 650 | 4 | |a phylogeny | |
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| 650 | 7 | |a Cytidine |2 NLM | |
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| 650 | 7 | |a APOBEC3F protein, human |2 NLM | |
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| 650 | 7 | |a Cytosine Deaminase |2 NLM | |
| 650 | 7 | |a EC 3.5.4.1 |2 NLM | |
| 700 | 1 | |a Raymond, Kyle A |e verfasserin |4 aut | |
| 700 | 1 | |a Boutin, Laetitia |e verfasserin |4 aut | |
| 700 | 1 | |a Guillier, Sophie |e verfasserin |4 aut | |
| 700 | 1 | |a Lemoine, Frédéric |e verfasserin |4 aut | |
| 700 | 1 | |a Ferraris, Olivier |e verfasserin |4 aut | |
| 700 | 1 | |a Tournier, Jean-Nicolas |e verfasserin |4 aut | |
| 700 | 1 | |a Iseni, Frédéric |e verfasserin |4 aut | |
| 700 | 1 | |a Simon-Lorière, Etienne |e verfasserin |4 aut | |
| 700 | 1 | |a Vartanian, Jean-Pierre |e verfasserin |4 aut | |
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