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

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

24 Scopus citations

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 (US)
Pages (from-to)	595-600
Number of pages	6
Journal	Science
Volume	382
Issue number	6670
DOIs	https://doi.org/10.1126/science.adg8116
State	Published - Nov 1 2023
Externally published	Yes

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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, 382(6670), 595-600. https://doi.org/10.1126/science.adg8116

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, vol. 382, no. 6670, pp. 595-600. https://doi.org/10.1126/science.adg8116

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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 ~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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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

PY - 2023/11/1

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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.

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

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