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

• 成果类型: Article
• 署名作者: O'Toole, Aine; Neher, Richard A.; Ndodo, Nnaemeka; Borges, Vitor; Gannon, Ben; Gomes, Joao 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
• 署名单位: University of Edinburgh; University of Basel; Swiss Institute of Bioinformatics; Instituto Nacional de Saude Dr. Ricardo Jorge; UK Health Security Agency (UKHSA); Lusofona University; Universidade de Lisboa; UK Health Security Agency (UKHSA); Defence Science & Technology Laboratory; KU Leuven; University of Birmingham; University of California System; University of California Los Angeles; University of Arizona
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11039
• DOI: 10.1126/science.adg8116
• 发表日期: 2023-11-03
• 页码: 595-600
• 关键词: dna; hypermutation; mitochondrial; population; EVOLUTION

摘要

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 similar to 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.