{
  "abstract": "African swine fever (ASF), caused by the ASF virus (ASFV), is a fatal hemorrhagic disease of domestic pigs that causes significant economic losses in the global pig industry. Systemic hemorrhages and abnormal coagulation of multiple tissues and organs are the typical lesions of ASFV infection, but the mechanism is still unknown. The exaggerated inflammation caused by ASFV infection is believed to contribute to endothelial injury and coagulopathy. Here, we demonstrate that circulating endothelial cells are significantly elevated in ASFV-infected pigs. In vitro infection assay shows that both primary and immortalized endothelial cells are permissive for ASFV replication, and ASFV infection triggers apoptosis of infected cells. ASFV disrupts redox homeostasis by negatively regulating the NRF2 pathway, which in turn leads to oxidative stress and ROS-mediated endothelial cell apoptosis. Mechanistically, ASFV D117L suppresses NRF2 signaling by interacting with KEAP1 and promoting the ubiquitination of NRF2. Functional analyses reveal that KEAP1 acts as a proviral factor for ASFV infection in endothelial cells, whereas its substrate, NRF2, suppresses viral replication. Further, pharmacological inhibition of KEAP1 by 4-Octyl itaconate (4-OI) and Sulforaphane (SFN) inhibits ASFV replication and ROS-dependent cell death. Our findings uncover a potential mechanism for endothelial dysfunction during ASFV infection and suggest that targeting KEAP1 to maintain endothelial redox homeostasis could be a promising approach for ASF treatment.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00018-026-06380-1.",
  "abstract_shown": true,
  "affiliations": [
    "College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan Province China",
    "State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou Veterinary Research Institute, Lanzhou University, Chinese Academy of Agricultural Sciences, Lanzhou, 730046 China",
    "Department of Pharmaceutical Sciences, Division of Pharmacognosy, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, Vienna, 1090 Austria",
    "Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou, 730046 China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Yumei Han"
    },
    {
      "affs": [
        1
      ],
      "name": "Fayu Yang"
    },
    {
      "affs": [
        1
      ],
      "name": "Wenchao Xue"
    },
    {
      "affs": [
        1
      ],
      "name": "Tianxing Cao"
    },
    {
      "affs": [
        1
      ],
      "name": "Xiaoyun Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Kunpeng Zhang"
    },
    {
      "affs": [
        1
      ],
      "name": "Yuxuan Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Zhonghui Zhang"
    },
    {
      "affs": [
        1
      ],
      "name": "Zhengshan Feng"
    },
    {
      "affs": [
        1
      ],
      "name": "Huanan Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Zhengwang Shi"
    },
    {
      "affs": [
        1
      ],
      "name": "Weijun Cao"
    },
    {
      "affs": [
        0
      ],
      "name": "Jun Zhao"
    },
    {
      "affs": [
        2
      ],
      "name": "Elke H Heiss"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Haixue Zheng"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Zixiang Zhu"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Shilei Zhang",
      "orcid": "0009-0001-8964-5264"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0jaet3ywyqxhf.bib",
  "cited_by": 0,
  "doi": "10.1007/s00018-026-06380-1",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13737249/",
  "id": "0jaet3ywyqxhf",
  "issns": [
    "1420-682X",
    "1420-9071"
  ],
  "landing_url": "https://doi.org/10.1007/s00018-026-06380-1",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "1103|Animal Disease Management and Epidemiology"
    ]
  ],
  "openalex": "W7201957891",
  "pdf_url": null,
  "pmcid": "PMC13737249",
  "pmid": "42982904",
  "published": "2026-08-08",
  "publisher": "Springer",
  "ris": "https://research.draconitic.com/paper/0jaet3ywyqxhf.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:22:29Z",
      "native_id": "PMC13737249",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s00018-026-06380-1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1103|Animal Disease Management and Epidemiology",
      "subfield": "zoology-behaviour"
    }
  ],
  "title": "ASFV D117L hijacks KEAP1 to induce oxidative stress-dependent vascular endothelial cell death",
  "title_text": "ASFV D117L hijacks KEAP1 to induce oxidative stress-dependent vascular endothelial cell death",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:22:29Z",
  "url": "https://research.draconitic.com/paper/0jaet3ywyqxhf",
  "venue": "Cellular and Molecular Life Sciences: CMLS",
  "versions": []
}