{
  "abstract": "Viral myocarditis involves overlapping viral infection, immune-mediated injury, cardiomyocyte stress, and remodeling. Extracellular vesicles (EVs) are increasingly investigated as mediators and biomarkers of these processes, but their interpretation and clinical translation depend on the identity and topology of associated proteins. This review examines EV-associated proteins, particularly membrane-associated and externally accessible proteins, as a framework for understanding viral dissemination, myocardial immune interactions, liquid biopsy, and therapeutic targeting. Direct mechanistic evidence is concentrated in coxsackievirus B3 (CVB3) models, where extracellular membrane-associated viral populations can facilitate non-lytic release, alter cellular tropism, permit entry into receptor-poor cells, and reduce susceptibility to neutralizing antibodies. Host receptors, HSP60, autophagy-associated LC3, viral capsid proteins, and EV cargo proteins offer distinct mechanistic and translational insights; these findings cannot automatically be extrapolated to other cardiotropic viruses. Candidate circulating EV-associated proteins and cardiomyocyte-associated EV capture markers show preliminary diagnostic promise, but current studies are limited by small cohorts, inconsistent disease definitions, sparse confirmation of viral etiology, insufficient particle characterization, and limited validation against clinically relevant disease controls. A key unresolved issue is protein topology: a protein detected in an EV-enriched lysate may be luminal, membrane-associated, externally accessible, or derived from co-isolated soluble proteins, lipoproteins, or virions. External epitope accessibility must be established before a candidate can be used for intact-EV capture or extracellular targeting. We distinguish direct myocarditis findings from evidence extrapolated from other disease models and assess EV–virion separation, particle identity, protein localization, cellular origin, immune recognition, and clinical validation. A protein-centered approach integrating orthogonal particle characterization, mechanistic perturbation, and prospective human studies is needed to determine whether EV-associated proteins can become clinically useful biomarkers or therapeutic targets in viral myocarditis.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Review",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "Zihao Chen"
    },
    {
      "name": "Zijun Qu"
    },
    {
      "name": "Ziheng Wang"
    },
    {
      "name": "Xin Wang"
    },
    {
      "name": "Hongyan Yao"
    },
    {
      "name": "Danxuan Zheng"
    },
    {
      "name": "Kun Lv"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3d4h06q7td4h3.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.2004445",
  "fulltext_url": null,
  "id": "3d4h06q7td4h3",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.2004445",
  "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": [
    [
      "feed-journal",
      "biology/immunology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-09",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/3d4h06q7td4h3.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:20:31Z",
      "native_id": "10.3389/fimmu.2026.2004445",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.2004445"
    },
    {
      "first_seen": "2026-11-09T12:22:59Z",
      "native_id": "10.3389/fimmu.2026.2004445",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.2004445/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "feed-journal:biology/immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Extracellular vesicle-associated proteins in viral myocarditis: surface topology, immune pathogenesis, and translational opportunities",
  "title_text": "Extracellular vesicle-associated proteins in viral myocarditis: surface topology, immune pathogenesis, and translational opportunities",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:22:59Z",
  "url": "https://research.draconitic.com/paper/3d4h06q7td4h3",
  "venue": "Frontiers in Immunology",
  "versions": []
}