{
  "abstract": "Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi sarcoma, a malignancy that primarily affects immunocompromised individuals, and is also linked to multiple other diseases. Progress in understanding KSHV pathogenesis and developing effective vaccines or therapies has been severely limited by the lack of a reliable in vivo model that recapitulates infection, persistence, and disease. Previous work suggested that the common marmoset (Callithrix jacchus), a small New World primate, can support KSHV infection and pathogenesis, but the reproducibility and utility of this model has not been rigorously established. Here, we sought to validate the common marmoset as a non-human primate model for KSHV studies by evaluating viral infection under both immunocompetent and immunosuppressed conditions. We first tested the use of intravenous and oral tacrolimus-based immunosuppression, confirming infection in challenged marmosets but also encountering tacrolimus dosing inconsistencies and toxicity. To overcome these limitations, we developed and validated a targeted immunosuppression approach using two novel mouse–marmoset chimeric monoclonal antibodies, anti-CD4 [TAWA] and anti-CD8 [OCHO], to selectively deplete T cell subsets. Altogether, we demonstrated across four independent experiments that KSHV can establish systemic infection in both immunocompetent and immunosuppressed conditions marmosets, evidenced by viremia in peripheral blood mononuclear cells, detectable seroconversion, and tissue persistence. The chimeric antibodies mediated efficient, subset‑specific depletion of CD4+ and CD8+ T cells and enabled a quantifiable, well‑tolerated immunosuppressive regimen. Moreover, we showed for the first time that monoclonal antibody-treated marmosets exhibit KSHV shedding in saliva and lytic replication, indicating that infection in this model is not merely latent but supports a full, human‑like replication cycle. Together these findings validate the common marmoset as a susceptible and translationally relevant non-human primate for studying KSHV infection and introduce a practical immunosuppressive tool for dissecting viral pathogenesis and immunity in vivo, providing a platform for testing vaccine and therapeutics. Author summary: Kaposi sarcoma-associated herpesvirus (KSHV) causes Kaposi sarcoma, a cancer that affects the skin and internal organs, and is associated with several other diseases that primarily occur in people with weakened immune systems. Studying KSHV has been difficult because the virus naturally infects humans, and suitable animal models are limited. Prior studies showed that common marmosets, a small type of monkey, can be experimentally infected with KSHV, but this animal model has remained underdeveloped. To improve this model, we carefully characterized KSHV infection in marmosets and generated new antibody-based tools to temporarily weaken (i.e., immunosuppress) their immune systems. Using these tools, we demonstrated that KSHV establishes long-term infection in both healthy and immunosuppressed marmosets. Importantly, we showed for the first time that immunosuppressed marmosets can shed KSHV virus in their saliva, indicating KSHV is actively replicating, similar to what is seen in infected humans. Our findings validate the marmoset as a relevant model for KSHV infection and provide a valuable platform in which to study viral biology and to evaluate vaccines and potential treatments.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Immuno-Oncology, Beckman Research Institute of City of Hope, Duarte, California, United States of America",
    "Irell & Manella Graduate School of Biological Sciences of City of Hope, Duarte, California, United States of America",
    "Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America",
    "Department of Microbial Sciences in Health, and Global Center for Pathogen and Human Health Research, Cleveland Clinic Research, Cleveland, Ohio, United States of America",
    "MassBiologics, UMass Chan Medical School, Boston, Massachusetts, United States of America",
    "Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas, United States of America"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Li Han"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Esther Rodriguez"
    },
    {
      "affs": [
        2
      ],
      "name": "Caitlin Shaw"
    },
    {
      "affs": [
        2
      ],
      "name": "Joe Kurian"
    },
    {
      "affs": [
        2
      ],
      "name": "Saverio Capuano"
    },
    {
      "affs": [
        0
      ],
      "name": "Gabriela M. Escalante"
    },
    {
      "affs": [
        0
      ],
      "name": "Murali Muniraju"
    },
    {
      "affs": [
        3
      ],
      "name": "Kyle Jung"
    },
    {
      "affs": [
        0
      ],
      "name": "Lorraine Z. Mutsvunguma"
    },
    {
      "affs": [
        4
      ],
      "name": "Kathleen Engelman"
    },
    {
      "affs": [
        3
      ],
      "name": "Jae Jung"
    },
    {
      "affs": [
        5
      ],
      "name": "Corinna N. Ross"
    },
    {
      "affs": [
        0
      ],
      "name": "Ivana G. Reidel"
    },
    {
      "affs": [
        0
      ],
      "name": "Javier Gordon Ogembo",
      "orcid": "0000-0001-6949-8693"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9cw89qnntgpr2.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.ppat.1014698",
  "fulltext_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014698",
  "id": "9cw89qnntgpr2",
  "issns": [
    "1553-7374",
    "1553-7366"
  ],
  "landing_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014698",
  "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": [
    [
      "heading",
      "Amniotes"
    ],
    [
      "heading",
      "Animal Models"
    ],
    [
      "heading",
      "Animal Studies"
    ],
    [
      "heading",
      "Animal cells"
    ],
    [
      "heading",
      "Animals"
    ],
    [
      "heading",
      "Biology and Life Sciences"
    ],
    [
      "heading",
      "Biology and life sciences"
    ],
    [
      "heading",
      "Blood cells"
    ],
    [
      "heading",
      "Cell biology"
    ],
    [
      "heading",
      "Cellular types"
    ],
    [
      "heading",
      "Clinical Medicine"
    ],
    [
      "heading",
      "Cytophotometry"
    ],
    [
      "heading",
      "Cytotoxic T cells"
    ],
    [
      "heading",
      "DNA viruses"
    ],
    [
      "heading",
      "Enzyme-Linked Immunoassays"
    ],
    [
      "heading",
      "Eukaryota"
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      "heading",
      "Experimental Organism Systems"
    ],
    [
      "heading",
      "Flow Cytometry"
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    [
      "heading",
      "Herpesviruses"
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    [
      "heading",
      "Immune Suppression"
    ],
    [
      "heading",
      "Immune cells"
    ],
    [
      "heading",
      "Immunoassays"
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    [
      "heading",
      "Immunologic Techniques"
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    [
      "heading",
      "Immunology"
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      "heading",
      "Kaposi's Sarcoma-Associated Herpesvirus"
    ],
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      "heading",
      "Mammals"
    ],
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      "Marmosets"
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    [
      "heading",
      "Medical Microbiology"
    ],
    [
      "heading",
      "Medicine and Health Sciences"
    ],
    [
      "heading",
      "Medicine and health sciences"
    ],
    [
      "heading",
      "Microbial Pathogens"
    ],
    [
      "heading",
      "Microbiology"
    ],
    [
      "heading",
      "Monkeys"
    ],
    [
      "heading",
      "New World monkeys"
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    [
      "heading",
      "Organisms"
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    [
      "heading",
      "Pathogens"
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      "heading",
      "Research and Analysis Methods"
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      "heading",
      "Signs and Symptoms"
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    [
      "heading",
      "Spectrophotometry"
    ],
    [
      "heading",
      "Spectrum Analysis Techniques"
    ],
    [
      "heading",
      "T cells"
    ],
    [
      "heading",
      "Vertebrates"
    ],
    [
      "heading",
      "Viral Load"
    ],
    [
      "heading",
      "Viral Pathogens"
    ],
    [
      "heading",
      "Viral Replication"
    ],
    [
      "heading",
      "Viral Transmission and Infection"
    ],
    [
      "heading",
      "Virology"
    ],
    [
      "heading",
      "Viruses"
    ],
    [
      "heading",
      "White blood cells"
    ],
    [
      "heading",
      "Zoology"
    ],
    [
      "openalex",
      "2730|Viral-associated cancers and disorders"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Blood cells/White blood cells/T cells/Cytotoxic T cells"
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      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Immune cells/White blood cells/T cells/Cytotoxic T cells"
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      "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Viral pathogens/Herpesviruses/Kaposi's sarcoma-associated herpesvirus"
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      "/Biology and life sciences/Microbiology/Virology/Viral replication"
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    [
      "plos",
      "/Biology and life sciences/Microbiology/Virology/Viral transmission and infection/Viral load"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Eukaryota/Animals/Vertebrates/Amniotes/Mammals/Primates/Monkeys/New World monkeys/Marmosets"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Viruses/DNA viruses/Herpesviruses/Kaposi's sarcoma-associated herpesvirus"
    ],
    [
      "plos",
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    ],
    [
      "plos",
      "/Biology and life sciences/Zoology/Animals/Vertebrates/Amniotes/Mammals/Primates/Monkeys/New World monkeys/Marmosets"
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      "/Medicine and health sciences/Clinical medicine/Signs and symptoms/Immune suppression"
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      "/Medicine and health sciences/Immunology/Immune suppression"
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    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Viral pathogens/Herpesviruses/Kaposi's sarcoma-associated herpesvirus"
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    [
      "plos",
      "/Research and analysis methods/Animal studies/Experimental organism systems/Animal models/Marmosets"
    ],
    [
      "plos",
      "/Research and analysis methods/Immunologic techniques/Immunoassays/Enzyme-linked immunoassays"
    ],
    [
      "plos",
      "/Research and analysis methods/Spectrum analysis techniques/Spectrophotometry/Cytophotometry/Flow cytometry"
    ]
  ],
  "openalex": "W7222880831",
  "pdf_url": "https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1014698&type=printable",
  "pmcid": "PMC13722297",
  "pmid": "42932380",
  "published": "2026-10-26",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/9cw89qnntgpr2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:17Z",
      "native_id": "10.1371/journal.ppat.1014698",
      "source": "plos",
      "url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014698"
    },
    {
      "first_seen": "2026-11-03T12:22:50Z",
      "native_id": "PMC13722297",
      "source": "pmc",
      "url": "https://doi.org/10.1371/journal.ppat.1014698"
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  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
    },
    {
      "field": "biology",
      "origin": "plos:immunology",
      "subfield": "immunology"
    },
    {
      "field": "biology",
      "origin": "plos:microbiology",
      "subfield": "microbiology"
    },
    {
      "field": "biology",
      "origin": "heading:Zoology",
      "subfield": "zoology-behaviour"
    },
    {
      "field": "medicine",
      "origin": "heading:Clinical Medicine",
      "subfield": "general"
    }
  ],
  "title": "Newly developed monoclonal antibodies for marmoset immunosuppression enable KSHV lytic replication and salivary shedding: A promising model for KSHV pathogenesis studies",
  "title_text": "Newly developed monoclonal antibodies for marmoset immunosuppression enable KSHV lytic replication and salivary shedding: A promising model for KSHV pathogenesis studies",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:22:50Z",
  "url": "https://research.draconitic.com/paper/9cw89qnntgpr2",
  "venue": "PLOS Pathogens",
  "versions": []
}