{
  "abstract": "Herpesvirus infection triggers excessive inflammation, contributing to tissue injury and disease severity, but the underlying drivers remain unclear. Here we identify EphA2 as a critical mediator of pseudorabies virus (PRV)-induced inflammatory response. Genetic or pharmacological inhibition of EphA2 reduced TNF-α production in PRV-infected cells and mice, alleviated liver and lung damage, and improved mice survival. Mechanistically, PRV infection promoted EphA2 phosphorylation at Ser-897, which activated NF-κB and MAPK pathways to drive TNF-α production. The PRV tegument protein UL40 directly bound the EphA2 kinase domain (residues 697–901), a region that also interacts with Akt. Unexpectedly, Akt acted as a negative regulator of inflammation, as its knockdown exacerbated cytokine production. UL40 competitively disrupted the constitutive EphA2–Akt complex in a time-dependent manner, relieving Akt-mediated restraint on EphA2 S897 phosphorylation. Accordingly, a UL40-deficient PRV mutant failed to enhance S897 phosphorylation, elicited lower inflammatory responses, and showed attenuated virulence in mice. Collectively, our findings reveal a proviral strategy whereby PRV UL40 hijacks EphA2 to counteract an intrinsic Akt-dependent inhibitory pathway. This UL40–EphA2–Akt cascade is a critical determinant of virus-induced inflammation, and EphA2 S897 represents a potential therapeutic target for mitigating alphaherpesvirus immunopathology.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "Yutong Tian"
    },
    {
      "name": "Hang Yin"
    },
    {
      "name": "Jiaxiang Fu"
    },
    {
      "name": "Qingqing Yang"
    },
    {
      "name": "Ru Yan"
    },
    {
      "name": "Yuqing Li"
    },
    {
      "name": "Chao Ye"
    },
    {
      "name": "Rendong Fang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e1zqfvr78aeg5.bib",
  "cited_by": 0,
  "doi": "10.1186/s13567-026-01829-4",
  "fulltext_url": null,
  "id": "e1zqfvr78aeg5",
  "issns": [
    "0928-4249",
    "1297-9716"
  ],
  "landing_url": "https://hal.science/hal-05731885v1",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "2713|Herpesvirus Infections and Treatments"
    ]
  ],
  "openalex": "W7204205554",
  "pdf_url": "https://hal.science/hal-05731885/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-31",
  "publisher": "BioMed Central",
  "ris": "https://research.draconitic.com/paper/e1zqfvr78aeg5.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:21Z",
      "native_id": "hal-05731885",
      "source": "hal",
      "url": "https://hal.science/hal-05731885v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Herpesvirus Infections and Treatments",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Pseudorabies virus pUL40 drives inflammatory signaling through competitive hijacking of EphA2 from the Akt–EphA2 interaction",
  "title_text": "Pseudorabies virus pUL40 drives inflammatory signaling through competitive hijacking of EphA2 from the Akt–EphA2 interaction",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:21Z",
  "url": "https://research.draconitic.com/paper/e1zqfvr78aeg5",
  "venue": "Veterinary Research",
  "versions": []
}