{
  "abstract": "Monkeypox virus (MPXV) is a zoonotic virus endemic to Africa that has recently re-emerged, becoming the first orthopoxvirus with sustained human-to-human transmission since smallpox eradication. The 2022 global epidemic of MPXV was caused by Clade IIb virus (lineage B.1) that derived from the lineage A endemic to West Africa through APOBEC3 microevolution 1–3 . Here, comparison of lineage B.1 virus with its closest earlier A.1 ancestor reveals that despite only 46 nucleotide differences, lineage B.1 has attenuating phenotypic changes. Both viruses replicated equivalently in cell culture, but B.1 had defects in long-range spread, which mapped to APOBEC3 mutation E353K in OPG057 (F13L). MPXV B.1 was also defective in innate immune control, inducing higher IFNβ and innate immune signalling gene expression, and showing reduced capacity to suppress interleukin-1β-mediated responses, which mapped to APOBEC3 mutation R48C in OPG047 (F3L). Finally, MPXV B.1 had reduced virulence in a mouse model of MPXV infection relative to the ancestral A.1 strain. Our work demonstrates that the 2022 global outbreak MPXV was intrinsically attenuated, with attenuating mutations that are absent in concurrent, more severe clade IIb outbreaks. Our data also reveal that APOBEC3 editing is a mechanism of MPXV phenotypic variation, potentially contributing to clade evolution and competition.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Infectious Diseases, King's College London, London, UK",
    "Department of Microbial Sciences, University of Surrey, Guildford, UK",
    "Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), Madrid, Spain",
    "The Pirbright Institute, Pirbright, UK",
    "Sir William Dunn School of Pathology, University of Oxford, Oxford, UK",
    "CBR Division, Defence Science and Technology Laboratory, Salisbury, UK",
    "Department of Microbial Sciences, University of Surrey, Guildford, UK. c.maluquerdemotes@surrey.ac.uk"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 21,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Rebecca P. Sumner",
      "orcid": "0000-0003-0735-8649"
    },
    {
      "affs": [
        1
      ],
      "name": "Lucy Eke",
      "orcid": "0009-0008-5325-1782"
    },
    {
      "affs": [
        2
      ],
      "name": "Bruno Hernáez",
      "orcid": "0000-0002-4351-0102"
    },
    {
      "affs": [
        1
      ],
      "name": "Alasdair J. M. Hood",
      "orcid": "0000-0003-1110-7957"
    },
    {
      "affs": [
        1
      ],
      "name": "Telma M Sancheira Freitas"
    },
    {
      "affs": [
        1
      ],
      "name": "Hannah Ashby"
    },
    {
      "affs": [
        1
      ],
      "name": "Ailish Ellis",
      "orcid": "0009-0008-4601-6426"
    },
    {
      "affs": [
        1
      ],
      "name": "Marine J. Petit",
      "orcid": "0000-0001-7427-7203"
    },
    {
      "affs": [
        1
      ],
      "name": "Sian Lant",
      "orcid": "0000-0001-7764-3520"
    },
    {
      "affs": [
        1
      ],
      "name": "Isobel Stokes",
      "orcid": "0000-0002-1833-2754"
    },
    {
      "affs": [
        1
      ],
      "name": "Preetam Parija"
    },
    {
      "affs": [
        2
      ],
      "name": "Isabel Alonso-Sánchez",
      "orcid": "0000-0002-6304-4938"
    },
    {
      "affs": [
        2
      ],
      "name": "Francisco Javier Alvarez-de Miranda",
      "orcid": "0000-0002-2854-2704"
    },
    {
      "affs": [
        2
      ],
      "name": "Alazne R. Unanue",
      "orcid": "0009-0006-6927-9996"
    },
    {
      "affs": [
        3
      ],
      "name": "Kevin Maringer",
      "orcid": "0000-0003-0977-8807"
    },
    {
      "affs": [
        3
      ],
      "name": "Isabelle Dietrich",
      "orcid": "0000-0002-6300-109X"
    },
    {
      "affs": [
        3
      ],
      "name": "Bryan Charleston",
      "orcid": "0000-0002-6952-9338"
    },
    {
      "affs": [
        4
      ],
      "name": "Geoffrey L. Smith",
      "orcid": "0000-0002-3730-9955"
    },
    {
      "affs": [
        5
      ],
      "name": "David Ulaeto",
      "orcid": "0000-0002-7493-3159"
    },
    {
      "affs": [
        2
      ],
      "name": "Antonio Alcamı́",
      "orcid": "0000-0002-3333-6016"
    },
    {
      "affs": [
        6
      ],
      "name": "Carlos Maluquer de Motes",
      "orcid": "0000-0003-4712-4601"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/69kgsz4q7evks.bib",
  "cited_by": 5,
  "doi": "10.1038/s41467-026-76580-7",
  "fulltext_url": null,
  "id": "69kgsz4q7evks",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://doi.org/10.1038/s41467-026-76580-7",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2406|Poxvirus research and outbreaks"
    ]
  ],
  "openalex": "W7202172697",
  "pdf_url": "https://www.nature.com/articles/s41467-026-76580-7_reference.pdf",
  "pmcid": "PMC13554265",
  "pmid": "42711302",
  "published": "2026-08-11",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/69kgsz4q7evks.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T13:20:55Z",
      "native_id": "W7202172697",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41467-026-76580-7"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2406|Poxvirus research and outbreaks",
      "subfield": "microbiology"
    }
  ],
  "title": "APOBEC3-driven attenuation of the 2022 global outbreak monkeypox virus relative to its clade IIb ancestor",
  "title_text": "APOBEC3-driven attenuation of the 2022 global outbreak monkeypox virus relative to its clade IIb ancestor",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:11Z",
  "url": "https://research.draconitic.com/paper/69kgsz4q7evks",
  "venue": "Nature Communications",
  "versions": []
}