APOBEC3 deaminase editing in mpox virus as evidence for sustained human transmission since at least 2016
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.18/8947 |
Resumo: | Historically, mpox has been characterized as an endemic zoonotic disease that transmits through contact with the reservoir rodent host in West and Central Africa. However, in May 2022, human cases of mpox were detected spreading internationally beyond countries with known endemic reservoirs. When the first cases from 2022 were sequenced, they shared 42 nucleotide differences from the closest mpox virus (MPXV) previously sampled. Nearly all these mutations are characteristic of the action of APOBEC3 deaminases, host enzymes with antiviral function. Assuming APOBEC3 editing is characteristic of human MPXV infection, we developed a dual-process phylogenetic molecular clock that-inferring a rate of ~6 APOBEC3 mutations per year-estimates that MPXV has been circulating in humans since 2016. These observations of sustained MPXV transmission present a fundamental shift to the perceived paradigm of MPXV epidemiology as a zoonosis and highlight the need for revising public health messaging around MPXV as well as outbreak management and control. |
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APOBEC3 deaminase editing in mpox virus as evidence for sustained human transmission since at least 2016Mpox VirusMonkeypox VirusGeneticsEpidemiologyTransmissionMutationPhylogenyAPOBEC DeaminasesHuman MPXV infectionInfecções EmergentesHistorically, mpox has been characterized as an endemic zoonotic disease that transmits through contact with the reservoir rodent host in West and Central Africa. However, in May 2022, human cases of mpox were detected spreading internationally beyond countries with known endemic reservoirs. When the first cases from 2022 were sequenced, they shared 42 nucleotide differences from the closest mpox virus (MPXV) previously sampled. Nearly all these mutations are characteristic of the action of APOBEC3 deaminases, host enzymes with antiviral function. Assuming APOBEC3 editing is characteristic of human MPXV infection, we developed a dual-process phylogenetic molecular clock that-inferring a rate of ~6 APOBEC3 mutations per year-estimates that MPXV has been circulating in humans since 2016. These observations of sustained MPXV transmission present a fundamental shift to the perceived paradigm of MPXV epidemiology as a zoonosis and highlight the need for revising public health messaging around MPXV as well as outbreak management and control.Editor’s summary: In March 2022, an international epidemic of human Mpox was detected, showing that it was not solely a zoonotic infection. A hallmark of the approximately 88,000 cases that have been reported were TC>TT and GA>AA mutations in Mpox viruses, which were acquired at a surprisingly high evolutionary rate for a pox virus. Knowing that these types of mutation are a sign of activity by a host antiviral enzyme called APOBEC3, O’Toole et al. investigated whether the mutations reflected human-to-human transmission rather than repeated zoonotic spillover. Bayesian evolutionary analysis showed that Mpox virus recently diversified into several lineages in humans that display elevated numbers of mutations, signaling APOBEC exposure and sustained human-to-human transmission rather than zoonosis as the source of new cases. —Caroline AshWellcome Trust ARTIC (Collaborators Award 206298/Z/17/Z, ARTIC network) (Á.O.T., P.L., M.A.S., A.R.); European Research Council (grant agreement no. 725422 – ReservoirDOCS) (P.L., M.A.S., A.R.); National Institutes of Health (R01 AI153044) (P.L., M.A.S., A.R.); David and Lucile Packard Foundation (M.W.); Research Foundation, Flanders– Fonds voor Wetenschappelijk Onderzoek–Vlaanderen, G066215N, G0D5117N and G0B9317N (P.L.); HORIZON 2020 EU grant 874850 MOOD (P.L.); HERA project (grant/2021/PHF/23776) supported by the European Commission through the European Centre for Disease Control and Prevention (V.B. and J.P.G.). The Nigeria Centre for Disease Control and Prevention receives core funding from the Nigerian government.American Association for the Advancement of ScienceRepositório Científico do Instituto Nacional de SaúdeO’Toole, ÁineNeher, Richard A.Ndodo, NnaemekaBorges, VitorGannon, BenGomes, João PauloGroves, NatalieKing, David J.Maloney, DanielLemey, PhilippeLewandowski, KuiamaLoman, NicholasMyers, RichardOmah, Ifeanyi F.Suchard, Marc A.Worobey, MichaelChand, MeeraIhekweazu, ChikweUlaeto, DavidAdetifa, IfedayoRambaut, Andrew2024-01-22T15:39:31Z2023-11-032023-11-03T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/8947engScience. 2023 Nov 3;382(6670):595-600. doi: 10.1126/science.adg8116. Epub 2023 Nov 2.0036-807510.1126/science.adg8116info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-01-27T01:31:47Zoai:repositorio.insa.pt:10400.18/8947Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T01:57:59.365088Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
APOBEC3 deaminase editing in mpox virus as evidence for sustained human transmission since at least 2016 |
title |
APOBEC3 deaminase editing in mpox virus as evidence for sustained human transmission since at least 2016 |
spellingShingle |
APOBEC3 deaminase editing in mpox virus as evidence for sustained human transmission since at least 2016 O’Toole, Áine Mpox Virus Monkeypox Virus Genetics Epidemiology Transmission Mutation Phylogeny APOBEC Deaminases Human MPXV infection Infecções Emergentes |
title_short |
APOBEC3 deaminase editing in mpox virus as evidence for sustained human transmission since at least 2016 |
title_full |
APOBEC3 deaminase editing in mpox virus as evidence for sustained human transmission since at least 2016 |
title_fullStr |
APOBEC3 deaminase editing in mpox virus as evidence for sustained human transmission since at least 2016 |
title_full_unstemmed |
APOBEC3 deaminase editing in mpox virus as evidence for sustained human transmission since at least 2016 |
title_sort |
APOBEC3 deaminase editing in mpox virus as evidence for sustained human transmission since at least 2016 |
author |
O’Toole, Áine |
author_facet |
O’Toole, Áine Neher, Richard A. Ndodo, Nnaemeka Borges, Vitor Gannon, Ben Gomes, João Paulo Groves, Natalie King, David J. Maloney, Daniel Lemey, Philippe Lewandowski, Kuiama Loman, Nicholas Myers, Richard Omah, Ifeanyi F. Suchard, Marc A. Worobey, Michael Chand, Meera Ihekweazu, Chikwe Ulaeto, David Adetifa, Ifedayo Rambaut, Andrew |
author_role |
author |
author2 |
Neher, Richard A. Ndodo, Nnaemeka Borges, Vitor Gannon, Ben Gomes, João Paulo Groves, Natalie King, David J. Maloney, Daniel Lemey, Philippe Lewandowski, Kuiama Loman, Nicholas Myers, Richard Omah, Ifeanyi F. Suchard, Marc A. Worobey, Michael Chand, Meera Ihekweazu, Chikwe Ulaeto, David Adetifa, Ifedayo Rambaut, Andrew |
author2_role |
author author author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Nacional de Saúde |
dc.contributor.author.fl_str_mv |
O’Toole, Áine Neher, Richard A. Ndodo, Nnaemeka Borges, Vitor Gannon, Ben Gomes, João Paulo Groves, Natalie King, David J. Maloney, Daniel Lemey, Philippe Lewandowski, Kuiama Loman, Nicholas Myers, Richard Omah, Ifeanyi F. Suchard, Marc A. Worobey, Michael Chand, Meera Ihekweazu, Chikwe Ulaeto, David Adetifa, Ifedayo Rambaut, Andrew |
dc.subject.por.fl_str_mv |
Mpox Virus Monkeypox Virus Genetics Epidemiology Transmission Mutation Phylogeny APOBEC Deaminases Human MPXV infection Infecções Emergentes |
topic |
Mpox Virus Monkeypox Virus Genetics Epidemiology Transmission Mutation Phylogeny APOBEC Deaminases Human MPXV infection Infecções Emergentes |
description |
Historically, mpox has been characterized as an endemic zoonotic disease that transmits through contact with the reservoir rodent host in West and Central Africa. However, in May 2022, human cases of mpox were detected spreading internationally beyond countries with known endemic reservoirs. When the first cases from 2022 were sequenced, they shared 42 nucleotide differences from the closest mpox virus (MPXV) previously sampled. Nearly all these mutations are characteristic of the action of APOBEC3 deaminases, host enzymes with antiviral function. Assuming APOBEC3 editing is characteristic of human MPXV infection, we developed a dual-process phylogenetic molecular clock that-inferring a rate of ~6 APOBEC3 mutations per year-estimates that MPXV has been circulating in humans since 2016. These observations of sustained MPXV transmission present a fundamental shift to the perceived paradigm of MPXV epidemiology as a zoonosis and highlight the need for revising public health messaging around MPXV as well as outbreak management and control. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-11-03 2023-11-03T00:00:00Z 2024-01-22T15:39:31Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.18/8947 |
url |
http://hdl.handle.net/10400.18/8947 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Science. 2023 Nov 3;382(6670):595-600. doi: 10.1126/science.adg8116. Epub 2023 Nov 2. 0036-8075 10.1126/science.adg8116 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
American Association for the Advancement of Science |
publisher.none.fl_str_mv |
American Association for the Advancement of Science |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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