{
  "abstract": "Background\n\nCytomegalovirus (CMV) is a common herpesvirus that establishes lifelong latency and becomes increasingly prevalent with age. To systematically delineate CMV-associated immune remodeling at single-cell resolution, we analysed six human cohorts (including two newly established cohorts) using single-cell RNA sequencing, T cell receptor (TCR) sequencing, and flow cytometry.Results\n\nWe identified novel CMV-associated changes in cell frequencies, including increases in GZMK⁺ CD8⁺ T cells and atypical B cells, and a reduction in CD56dim NK cells, in addition to the canonical expansion of CD4⁺/CD8⁺ TEMRA and adaptive NK cells. Longitudinal profiling of an individual who seroconverted revealed rapid CMV-driven shifts in circulating immune cell frequencies. Leveraging a recently published CMV-specific TCRβ database, combined with predictive modeling (CMVerify), we identified novel CMV-specific clonal expansions that were reproduced across two independent cohorts. In the CD8⁺ lineage, CMV-specific clones were enriched in GZMK⁺ CD8⁺ T cells and CD8⁺ TEMRA cells, whereas in the CD4⁺ lineage, Th1 cells showed clonal expansion alongside CD4⁺ TEMRA cells.Conclusions\n\nThis multi-cohort integrative study defines the cellular and clonal signatures of latent CMV in humans and identifies GZMK⁺ CD8⁺ T cells and Th1 cells as previously underappreciated components of the CMV response.",
  "abstract_shown": true,
  "affiliations": [
    "The Jackson Laboratory for Genomic Medicine, Farmington, CT, 06032, USA.",
    "University of Connecticut School of Medicine, Farmington, CT, 06030, USA.",
    "Health Sciences North Research Institute, NOSM University, Sudbury, ON, P3E 2H3, Canada.",
    "Department of Medicine, McMaster University, Hamilton, ON, L8S 4L8, Canada.",
    "GRECC, Durham VA Health Care System, Durham, NC, 27705, USA.",
    "Department of Medicine and Duke Center for the Study of Aging and Human Development (Aging Center), Duke University School of Medicine, Durham, NC, 27705, USA.",
    "Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.",
    "Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.",
    "Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.",
    "The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.",
    "Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.",
    "The Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.",
    "Department of Pathology, Yale School of Medicine, New Haven, CT, 06510-3222, USA.",
    "The Jackson Laboratory for Genomic Medicine, Farmington, CT, 06032, USA. jacques.banchereau@gmail.com.",
    "Immunoledge LLC, Montclair, NJ, 07042, USA. jacques.banchereau@gmail.com.",
    "University of Connecticut School of Medicine, Farmington, CT, 06030, USA. kuchel@uchc.edu.",
    "UConn Center On Aging, University of Connecticut School of Medicine, Farmington, CT, 06030, USA. kuchel@uchc.edu.",
    "The Jackson Laboratory for Genomic Medicine, Farmington, CT, 06032, USA. duygu.ucar@jax.org.",
    "Institute for Systems Genomics, University of Connecticut Health Center, Farmington, CT, 06030, USA. duygu.ucar@jax.org."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Titas Grabauskas"
    },
    {
      "affs": [
        0
      ],
      "name": "Luke Trinity"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Chris P Verschoor"
    },
    {
      "affs": [
        0
      ],
      "name": "Djamel Nehar-Belaid"
    },
    {
      "affs": [
        0
      ],
      "name": "Radu Marches"
    },
    {
      "affs": [
        0
      ],
      "name": "Giray Eryilmaz"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Avinash S Mahajan"
    },
    {
      "affs": [
        0
      ],
      "name": "Sathyabaarathi Ravichandran"
    },
    {
      "affs": [
        0
      ],
      "name": "Asa Thibodeau"
    },
    {
      "affs": [
        2
      ],
      "name": "Emilie Picard"
    },
    {
      "affs": [
        1
      ],
      "name": "Chia-Ling Kuo"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Kenneth E Schmader"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Cathleen Colon-Emeric"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Heather E Whitson"
    },
    {
      "affs": [
        0
      ],
      "name": "Silke Paust"
    },
    {
      "affs": [
        6,
        7,
        8,
        9,
        10,
        11
      ],
      "name": "Adolfo García-Sastre"
    },
    {
      "affs": [
        12
      ],
      "name": "Gur Yaari"
    },
    {
      "affs": [
        13,
        14
      ],
      "name": "Jacques Banchereau"
    },
    {
      "affs": [
        15,
        16
      ],
      "name": "George A Kuchel"
    },
    {
      "affs": [
        17,
        18
      ],
      "name": "Duygu Ucar"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5m5tepvw0bhw7.bib",
  "cited_by": 2,
  "doi": "10.1186/s13059-026-04198-5",
  "fulltext_url": "https://europepmc.org/articles/PMC13721549",
  "id": "5m5tepvw0bhw7",
  "issns": [
    "1474-7596",
    "1474-760X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42958310",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2713|Cytomegalovirus and herpesvirus research"
    ]
  ],
  "openalex": "W7172333556",
  "pdf_url": "https://europepmc.org/articles/PMC13721549?pdf=render",
  "pmcid": "PMC13721549",
  "pmid": "42958310",
  "published": "2026-08-04",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/5m5tepvw0bhw7.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:29Z",
      "native_id": "MED:42958310",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42958310"
    },
    {
      "first_seen": "2026-11-03T12:22:13Z",
      "native_id": "PMC13721549",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s13059-026-04198-5"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Cytomegalovirus and herpesvirus research",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "CMV-specific clonal expansion in human Th1 and GZMK⁺ CD8⁺ T cells.",
  "title_text": "CMV-specific clonal expansion in human Th1 and GZMK⁺ CD8⁺ T cells.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:22:13Z",
  "url": "https://research.draconitic.com/paper/5m5tepvw0bhw7",
  "venue": "Genome biology",
  "versions": []
}