{
  "abstract": "Background: Chronic active Epstein-Barr virus disease (CAEBV) is a rare EBV-associated T/NK-cell lymphoproliferative disorder characterized by persistent viral infection, systemic inflammation, and highly variable clinical courses. Patients may develop HLH-like hyperinflammation, severe organ involvement, lymphoma transformation, or death, yet current assessment does not fully explain why patients with similar viral burden follow divergent trajectories.\n\nMethods: We integrated PBMC single-cell RNA-sequencing profiles from healthy controls and CAEBV samples with a retrospective cohort of 130 independent CAEBV patients to connect cellular immune remodeling with clinically measurable features.\n\nResults: Single-cell analysis identified T/NK remodeling toward cytotoxic, exhaustion-associated, senescence-associated, and metabolically altered states, accompanied by IFN-responsive, antigen-presenting myeloid programs. Ligand-receptor and receiver-side analyses prioritized candidate IFNγ-associated T/NK-to-myeloid communication within this IFN-responsive program, linking NK and CD8+ T-cell states with myeloid inflammatory activation. Guided by these findings, we mapped inflammatory, metabolic, coagulation, and lymphocyte-subset variables into a biology-informed clinical immunometabolic index reflecting inflammatory cytokine activation, metabolic stress, and adaptive immune contraction. Internally defined index strata were associated with increasing CAEBV+HLH, death, and severe-disease burden. Unsupervised clinical mapping further identified three exploratory but interpretable immunometabolic patterns, including immune-metabolically preserved, intermediate immune-contraction, and IFNγ-high immunometabolic high-risk, with distinct immune-cell, inflammatory, metabolic, and outcome profiles.\n\nConclusions: Together, these findings organize CAEBV heterogeneity around linked T/NK remodeling, myeloid activation, and systemic immunometabolic stress. This single-cell-informed clinical-pattern map complements EBV-DNA and organ-size assessment and supports prospective validation of clinically measurable, mechanism-guided monitoring and intervention strategies.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University",
    "Shanghai Sci-Tech Inno Center for Infection & Immunity",
    "Key Laboratory of Medical Molecular Virology (MOE/MOH), Shanghai Medical College, Fudan University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yue Cao"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhe Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Shenglei Yu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yanying Liang"
    },
    {
      "affs": [
        0
      ],
      "name": "Chenxi Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Xvrong Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Zenghui Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jianming Zheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Qiaoling Ruan"
    },
    {
      "affs": [
        0
      ],
      "name": "Yan Gao"
    },
    {
      "affs": [
        0
      ],
      "name": "Qingluan Yang"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Lingyun Shao"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Wenhong Zhang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/91s4a4cg6s22s.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1928095",
  "fulltext_url": null,
  "id": "91s4a4cg6s22s",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1928095/full",
  "language": null,
  "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": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-03",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/91s4a4cg6s22s.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T12:21:20Z",
      "native_id": "10.3389/fimmu.2026.1928095",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1928095/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "issn:1664-3224",
      "subfield": "immunology"
    }
  ],
  "title": "T/NK-cell remodeling and IFN-responsive myeloid activation delineate immunometabolic risk profiles in chronic active Epstein-Barr virus disease",
  "title_text": "T/NK-cell remodeling and IFN-responsive myeloid activation delineate immunometabolic risk profiles in chronic active Epstein-Barr virus disease",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T00:21:02Z",
  "url": "https://research.draconitic.com/paper/91s4a4cg6s22s",
  "venue": "Frontiers in Immunology",
  "versions": []
}