APOBEC3 deaminase editing in mpox virus as evidence for sustained human transmission since at least 2016

Áine O'Toole; Richard A. Neher; Nnaemeka Ndodo; Vitor Borges; Ben Gannon; João Paulo Gomes; Natalie Groves; David J. King; Daniel Maloney; Philippe Lemey; Kuiama Lewandowski; Nicholas Loman; Richard Myers; Ifeanyi F. Omah; Marc A. Suchard; Michael Worobey; Meera Chand; Chikwe Ihekweazu; David Ulaeto; Ifedayo Adetifa; Andrew Rambaut

doi:10.1126/science.adg8116

APOBEC3 deaminase editing in mpox virus as evidence for sustained human transmission since at least 2016

Áine O'Toole^*, Richard A. Neher, Nnaemeka Ndodo, Vitor Borges, Ben Gannon, João Paulo Gomes, Natalie Groves, David J. King, Daniel Maloney, Philippe Lemey, Kuiama Lewandowski, Nicholas Loman, Richard Myers, Ifeanyi F. Omah, Marc A. Suchard, Michael Worobey, Meera Chand, Chikwe Ihekweazu, David Ulaeto, Ifedayo AdetifaAndrew Rambaut^*

^*Corresponding author for this work

School of Biological Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	595-600
Number of pages	6
Journal	Science (New York, N.Y.)
Volume	382
Issue number	6670
DOIs	https://doi.org/10.1126/science.adg8116
Publication status	Published - 3 Nov 2023

Keywords / Materials (for Non-textual outputs)

Animals
Humans
Africa, Central/epidemiology
Africa, Western/epidemiology
APOBEC Deaminases/genetics
Disease Outbreaks
Mpox (monkeypox)/epidemiology
Monkeypox virus/genetics
Mutation
Phylogeny
Viral Zoonoses/genetics
RNA Editing

Access to Document

10.1126/science.adg8116Licence: Other

adg8116_final_combinedAccepted author manuscript, 3.15 MBLicence: Creative Commons: Attribution (CC-BY)
science.adg8116
License information: Copyright © 2023 the authors, some rights reserved, including, where applicable, UK Crown copyright licensed under the Open Government License v.3.0; exclusive licensee American Association for the Advancement of Science. No claim to original US government works. https://www.science.org/about/science-licenses-journal-article-reuse.
Final published version, 1.22 MBLicence: Other

The evolutionary dynamics of pathogen emergence and establishment: from Reservoir Detection to Outbreak Control
Rambaut, A. (Principal Investigator)
EU government bodies
1/08/17 → 31/07/23
Project: Research
Putting genomic surveillance at the heart of viral epidemic response.
Rambaut, A. (Principal Investigator)
UK-based charities
1/08/17 → 31/07/24
Project: Research

hmpxv/apobec3: v1.0.1
Rambaut, A. (Creator) & O'Toole, Á. (Creator), Zenodo, 10 Aug 2023
DOI: 10.5281/zenodo.8234484
Dataset

Cite this

O'Toole, Á., Neher, R. A., Ndodo, N., Borges, V., Gannon, B., Gomes, J. P., Groves, N., King, D. J., Maloney, D., Lemey, P., Lewandowski, K., Loman, N., Myers, R., Omah, I. F., Suchard, M. A., Worobey, M., Chand, M., Ihekweazu, C., Ulaeto, D., ... Rambaut, A. (2023). APOBEC3 deaminase editing in mpox virus as evidence for sustained human transmission since at least 2016. Science (New York, N.Y.), 382(6670), 595-600. https://doi.org/10.1126/science.adg8116

@article{c04a5bba4cb94468b00a0ea459de3fb0,

title = "APOBEC3 deaminase editing in mpox virus as evidence for sustained human transmission since at least 2016",

abstract = "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 \textasciitilde{}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.",

keywords = "Animals, Humans, Africa, Central/epidemiology, Africa, Western/epidemiology, APOBEC Deaminases/genetics, Disease Outbreaks, Mpox (monkeypox)/epidemiology, Monkeypox virus/genetics, Mutation, Phylogeny, Viral Zoonoses/genetics, RNA Editing",

author = "{\'A}ine O'Toole and Neher, \{Richard A.\} and Nnaemeka Ndodo and Vitor Borges and Ben Gannon and Gomes, \{Jo{\~a}o Paulo\} and Natalie Groves and King, \{David J.\} and Daniel Maloney and Philippe Lemey and Kuiama Lewandowski and Nicholas Loman and Richard Myers and Omah, \{Ifeanyi F.\} and Suchard, \{Marc A.\} and Michael Worobey and Meera Chand and Chikwe Ihekweazu and David Ulaeto and Ifedayo Adetifa and Andrew Rambaut",

note = "We thank those involved in sequencing MPXV genome sequences and shared data online rapidly, facilitating rapid public health responses, and also those who have continued to contribute to open science by sharing their data in open access platforms such as GenBank. We have provided all data and scripts related to this manuscript on Zenodo (36)",

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day = "3",

doi = "10.1126/science.adg8116",

language = "English",

volume = "382",

pages = "595--600",

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O'Toole, Á, Neher, RA, Ndodo, N, Borges, V, Gannon, B, Gomes, JP, Groves, N, King, DJ, Maloney, D, Lemey, P, Lewandowski, K, Loman, N, Myers, R, Omah, IF, Suchard, MA, Worobey, M, Chand, M, Ihekweazu, C, Ulaeto, D, Adetifa, I & Rambaut, A 2023, 'APOBEC3 deaminase editing in mpox virus as evidence for sustained human transmission since at least 2016', Science (New York, N.Y.), vol. 382, no. 6670, pp. 595-600. https://doi.org/10.1126/science.adg8116

TY - JOUR

T1 - APOBEC3 deaminase editing in mpox virus as evidence for sustained human transmission since at least 2016

AU - O'Toole, Áine

AU - Neher, Richard A.

AU - Ndodo, Nnaemeka

AU - Borges, Vitor

AU - Gannon, Ben

AU - Gomes, João Paulo

AU - Groves, Natalie

AU - King, David J.

AU - Maloney, Daniel

AU - Lemey, Philippe

AU - Lewandowski, Kuiama

AU - Loman, Nicholas

AU - Myers, Richard

AU - Omah, Ifeanyi F.

AU - Suchard, Marc A.

AU - Worobey, Michael

AU - Chand, Meera

AU - Ihekweazu, Chikwe

AU - Ulaeto, David

AU - Adetifa, Ifedayo

AU - Rambaut, Andrew

N1 - We thank those involved in sequencing MPXV genome sequences and shared data online rapidly, facilitating rapid public health responses, and also those who have continued to contribute to open science by sharing their data in open access platforms such as GenBank. We have provided all data and scripts related to this manuscript on Zenodo (36)

PY - 2023/11/3

Y1 - 2023/11/3

N2 - 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.

AB - 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.

KW - Animals

KW - Humans

KW - Africa, Central/epidemiology

KW - Africa, Western/epidemiology

KW - APOBEC Deaminases/genetics

KW - Disease Outbreaks

KW - Mpox (monkeypox)/epidemiology

KW - Monkeypox virus/genetics

KW - Mutation

KW - Phylogeny

KW - Viral Zoonoses/genetics

KW - RNA Editing

U2 - 10.1126/science.adg8116

DO - 10.1126/science.adg8116

M3 - Article

C2 - 37917680

SN - 0036-8075

VL - 382

SP - 595

EP - 600

JO - Science (New York, N.Y.)

JF - Science (New York, N.Y.)

IS - 6670

ER -

APOBEC3 deaminase editing in mpox virus as evidence for sustained human transmission since at least 2016

Abstract

Keywords / Materials (for Non-textual outputs)

Access to Document

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Projects

The evolutionary dynamics of pathogen emergence and establishment: from Reservoir Detection to Outbreak Control

Putting genomic surveillance at the heart of viral epidemic response.

Datasets

hmpxv/apobec3: v1.0.1

Cite this