{
  "abstract": "Gammaherpesviruses, including human Epstein-Barr Virus (EBV) and Kaposi’s Sarcoma-associated Herpesvirus (KSHV), establish lifelong latent infections that contribute to multiple cancers and Multiple Sclerosis. These viruses colonize naïve B cells and drive a robust, polyclonal germinal center response to expand the latent viral reservoir and establish lifelong infection in memory B cells. Despite the clinical burden of these viruses, the host factors that support chronic infection remain poorly defined. Interleukin-22 (IL-22) is a critical cytokine traditionally recognized for its protective roles in bacterial and fungal defense; however, its involvement in gammaherpesvirus pathogenesis has not been explored. Using murine gammaherpesvirus 68 (MHV68) as a tractable in vivo model, we identify IL-22 as a host factor that promotes the establishment of chronic gammaherpesvirus infection. MHV68 infection triggers robust IL-22 production across multiple anatomical sites and immune cell populations. Although IL-22 deficiency did not affect acute viral replication, IL-22-/- mice exhibited a sustained reduction in latent viral burden within both the spleen and peritoneal cavity. This phenotype was accompanied by impaired germinal center B cell and T follicular helper cell responses, reduced plasma-cell expansion, diminished virus-specific antibody responses, and attenuated polyclonal autoreactive antibody production. Furthermore, IL-22 deficiency was associated with reduced systemic BAFF levels, suggesting that IL-22 contributes to the establishment of a germinal center microenvironment that supports chronic infection. Together, these findings identify IL-22 as a previously unrecognized regulator of chronic gammaherpesvirus infection and reveal a role for this cytokine in coordinating germinal center responses, humoral immunity, and latent reservoir establishment, providing new insight into how host immune pathways contribute to lifelong gammaherpesvirus infection. Author summary: Gammaherpesviruses are double-stranded DNA viruses that establish lifelong infections in over 95% of adults worldwide and are associated with multiple cancers and autoimmune disease. To persist within the host, these viruses exploit germinal center B cells to establish a long-lived latent reservoir. Although the cytokine IL-22 is best known for its protective role in bacterial and fungal infections, its contribution to gammaherpesvirus infection was unknown. Using a murine model of gammaherpesvirus infection, we demonstrate that IL-22 promotes the establishment of chronic gammaherpesvirus infection without affecting acute viral replication. Mice lacking IL-22 exhibited reduced latent viral burden accompanied by impaired germinal center and plasma-cell responses along with diminished virus-specific and polyclonal antibody production. These findings suggest that IL-22 helps create an immune environment that favors viral latency. Our work identifies a previously unrecognized role for IL-22 in supporting chronic gammaherpesvirus infection and provides new insights into how host immune pathways contribute to lifelong gammaherpesvirus infection.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Investigative Medicine and Center for Immunobiology, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, Michigan, United States of America"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Sheikh Tahir Majeed"
    },
    {
      "name": "Samantha M. Bradford"
    },
    {
      "name": "Christopher N. Jondle"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f2gw247337yb6.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.ppat.1014016",
  "fulltext_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014016",
  "id": "f2gw247337yb6",
  "issns": [
    "1553-7374"
  ],
  "landing_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014016",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2730|Viral-associated cancers and disorders"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Immune system proteins/Antibodies"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Blood cells/White blood cells/B cells"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Immune cells/Antibody-producing cells/B cells"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Immune cells/White blood cells/B cells"
    ],
    [
      "plos",
      "/Biology and life sciences/Immunology/Immune cells/Antibody-producing cells/B cells"
    ],
    [
      "plos",
      "/Biology and life sciences/Immunology/Immune cells/White blood cells/B cells"
    ],
    [
      "plos",
      "/Biology and life sciences/Immunology/Immune response/Antibody response"
    ],
    [
      "plos",
      "/Biology and life sciences/Immunology/Immune system proteins/Antibodies"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Viral pathogens/Herpesviruses"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Virology/Viral persistence and latency"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Virology/Viral replication"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Viruses/DNA viruses/Herpesviruses"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Viruses/Viral pathogens/Herpesviruses"
    ],
    [
      "plos",
      "/Biology and life sciences/Physiology/Immune physiology/Antibodies"
    ],
    [
      "plos",
      "/Biology and life sciences/Physiology/Immune physiology/Spleen"
    ],
    [
      "plos",
      "/Medicine and health sciences/Immunology/Immune cells/Antibody-producing cells/B cells"
    ],
    [
      "plos",
      "/Medicine and health sciences/Immunology/Immune cells/White blood cells/B cells"
    ],
    [
      "plos",
      "/Medicine and health sciences/Immunology/Immune response/Antibody response"
    ],
    [
      "plos",
      "/Medicine and health sciences/Immunology/Immune system proteins/Antibodies"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Viral pathogens/Herpesviruses"
    ],
    [
      "plos",
      "/Research and analysis methods/Immunologic techniques/Immunoassays/Enzyme-linked immunoassays"
    ]
  ],
  "openalex": "W7211931685",
  "pdf_url": "https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1014016&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-08",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/f2gw247337yb6.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:56Z",
      "native_id": "10.1371/journal.ppat.1014016",
      "source": "plos",
      "url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014016"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "IL-22 promotes the establishment of chronic gammaherpesvirus infection by supporting the germinal center response",
  "title_text": "IL-22 promotes the establishment of chronic gammaherpesvirus infection by supporting the germinal center response",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:56Z",
  "url": "https://research.draconitic.com/paper/f2gw247337yb6",
  "venue": "PLOS Pathogens",
  "versions": []
}