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

Author:

O’Toole Áine1ORCID,Neher Richard A.2ORCID,Ndodo Nnaemeka3ORCID,Borges Vitor4ORCID,Gannon Ben5ORCID,Gomes João Paulo46ORCID,Groves Natalie7ORCID,King David J.8ORCID,Maloney Daniel1,Lemey Philippe9ORCID,Lewandowski Kuiama5,Loman Nicholas710ORCID,Myers Richard7ORCID,Omah Ifeanyi F.111,Suchard Marc A.12ORCID,Worobey Michael13ORCID,Chand Meera714,Ihekweazu Chikwe3,Ulaeto David7,Adetifa Ifedayo3ORCID,Rambaut Andrew1ORCID

Affiliation:

1. Institute of Ecology and Evolution, University of Edinburgh, Edinburgh EH9 3FL, UK.

2. Biozentrum, University of Basel and Swiss Institute of Bioinformatics, Basel, Switzerland.

3. Nigeria Centers for Disease Control and Prevention, Abuja, Nigeria.

4. National Institute of Health Doutor Ricardo Jorge (INSA), Lisbon, Portugal.

5. UK Health Security Agency, Porton Down, Salisbury SP4 0JG, UK.

6. Veterinary and Animal Research Centre (CECAV), Faculty of Veterinary Medicine, Lusófona University, Lisbon, Portugal.

7. UK Health Security Agency, London E14 5EA, UK.

8. CBR Division, Defence Science and Technology Laboratory, Salisbury SP4 0JQ, UK.

9. Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Leuven, Belgium.

10. University of Birmingham, Birmingham B15 2TT, UK.

11. Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka, Anambra State, Nigeria.

12. Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA 90095, USA.

13. Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85719, USA.

14. UKHSA Guys and St Thomas’ NHS Trust, London SE1 7EH, UK.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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