{
  "abstract": "Innate immunity constitutes the body’s first line of defense against pathogenic challenge, serving not only as a physical and cellular bulwark that rapidly curbs microbial proliferation but also as the essential rheostat that orchestrates downstream adaptive immune responses. Here, we identified MARK3, a serine/threonine protein kinase of the conserved MARK family, as a crucial regulator of innate antiviral immunity that promotes type I interferon (IFN-I) production in a kinase-dependent manner. Using both in vitro and in vivo models, we demonstrate that MARK3 exerts broad-spectrum antiviral activity via a signaling axis involving GEF-H1 and TBK1. Mechanistically, MARK3 directly interacts with GEF-H1 and phosphorylates it at Ser645. This phosphorylation event potentiates the activation of TBK1, leading to enhanced IRF3 phosphorylation. Activated IRF3 then translocates to the nucleus, where it triggers potent IFN-I induction and the downstream expression of interferon-stimulated genes (ISGs). Our study establishes MARK3 as an important antiviral kinase and defines the MARK3–GEF-H1–TBK1 axis as a novel signaling pathway driving interferon-mediated antiviral defense. Author summary: The innate immune system serves as the body’s first line of defense against viral pathogens, acting to curb infection at its earliest stages. In this study, we identified MARK3 as a candidate GEF-H1–interacting kinase and further showed that it enhances innate antiviral immunity in a kinase-dependent manner. Using both in vitro and in vivo models, we demonstrate that MARK3 binds to and phosphorylates GEF-H1 at Ser645, which in turn promotes TBK1 and IRF3 phosphorylation, driving robust activation of type I interferons to reinforce the host antiviral response.",
  "abstract_shown": true,
  "affiliations": [
    "Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu, China",
    "Department of Microbiology and Biotechnology, College of Life Sciences, Anhui Medical University, Hefei, China",
    "Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China",
    "Anhui Public Health Clinical Center, Hefei, China",
    "School of Biological and Environmental Engineering, Jingdezhen University, Jingdezhen, China"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xingmei Qi"
    },
    {
      "affs": [
        0
      ],
      "name": "Xue Zhu"
    },
    {
      "affs": [
        1,
        2,
        3
      ],
      "name": "Wenbiao Peng"
    },
    {
      "affs": [
        1,
        2,
        3
      ],
      "name": "Luoxue Hua"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Xinru Xie"
    },
    {
      "affs": [
        4
      ],
      "name": "Chuncan Si"
    },
    {
      "affs": [
        1
      ],
      "name": "Meimei Lan"
    },
    {
      "affs": [
        1
      ],
      "name": "Zifan Zhuang"
    },
    {
      "affs": [
        1
      ],
      "name": "Siyi Ding"
    },
    {
      "affs": [
        1
      ],
      "name": "Ting Xu"
    },
    {
      "affs": [
        1
      ],
      "name": "Junjie Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Yundi Zhang"
    },
    {
      "affs": [
        1
      ],
      "name": "Yifan Song"
    },
    {
      "affs": [
        1
      ],
      "name": "Yiping Yang"
    },
    {
      "affs": [
        1
      ],
      "name": "Yixue Cheng"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Tao Guo"
    },
    {
      "affs": [
        1,
        2,
        3
      ],
      "name": "Linchao Li"
    },
    {
      "affs": [
        1,
        2,
        3
      ],
      "name": "Kezhen Wang",
      "orcid": "0000-0003-0530-7098"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3bybgwfxyvpbr.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.ppat.1014701",
  "fulltext_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014701",
  "id": "3bybgwfxyvpbr",
  "issns": [
    "1553-7374",
    "1553-7366"
  ],
  "landing_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014701",
  "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",
      "Antiviral Immune Response"
    ],
    [
      "heading",
      "Biochemistry"
    ],
    [
      "heading",
      "Biology and Life Sciences"
    ],
    [
      "heading",
      "Biology and life sciences"
    ],
    [
      "heading",
      "Gene Expression"
    ],
    [
      "heading",
      "Genetics"
    ],
    [
      "heading",
      "Immune Response"
    ],
    [
      "heading",
      "Immunology"
    ],
    [
      "heading",
      "Immunoprecipitation"
    ],
    [
      "heading",
      "Interferons"
    ],
    [
      "heading",
      "Medical Microbiology"
    ],
    [
      "heading",
      "Medicine and Health Sciences"
    ],
    [
      "heading",
      "Microbial Genetics"
    ],
    [
      "heading",
      "Microbial Pathogens"
    ],
    [
      "heading",
      "Microbiology"
    ],
    [
      "heading",
      "Molecular Biology"
    ],
    [
      "heading",
      "Molecular Biology Techniques"
    ],
    [
      "heading",
      "Organisms"
    ],
    [
      "heading",
      "Pathogens"
    ],
    [
      "heading",
      "Pathology and Laboratory Medicine"
    ],
    [
      "heading",
      "Phosphorylation"
    ],
    [
      "heading",
      "Post-Translational Modification"
    ],
    [
      "heading",
      "Precipitation Techniques"
    ],
    [
      "heading",
      "Proteins"
    ],
    [
      "heading",
      "RNA viruses"
    ],
    [
      "heading",
      "Research Article"
    ],
    [
      "heading",
      "Research and Analysis Methods"
    ],
    [
      "heading",
      "Rhabdoviruses"
    ],
    [
      "heading",
      "Transfection"
    ],
    [
      "heading",
      "Vesicular Stomatitis Virus"
    ],
    [
      "heading",
      "Viral Gene Expression"
    ],
    [
      "heading",
      "Viral Genetics"
    ],
    [
      "heading",
      "Viral Pathogens"
    ],
    [
      "heading",
      "Viral Replication"
    ],
    [
      "heading",
      "Virology"
    ],
    [
      "heading",
      "Viruses"
    ],
    [
      "openalex",
      "2403|interferon and immune responses"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Interferons"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Post-translational modification/Phosphorylation"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Gene expression/Viral gene expression"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Microbial genetics/Viral genetics/Viral gene expression"
    ],
    [
      "plos",
      "/Biology and life sciences/Immunology/Immune response/Antiviral immune response"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Viral pathogens/Vesicular stomatitis virus"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Virology/Viral genetics/Viral gene expression"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Virology/Viral replication"
    ],
    [
      "plos",
      "/Biology and life sciences/Molecular biology/Molecular biology techniques/Transfection"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Viruses/RNA viruses/Rhabdoviruses/Vesicular stomatitis virus"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Viruses/Viral pathogens/Vesicular stomatitis virus"
    ],
    [
      "plos",
      "/Medicine and health sciences/Immunology/Immune response/Antiviral immune response"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Viral pathogens/Vesicular stomatitis virus"
    ],
    [
      "plos",
      "/Research and analysis methods/Molecular biology techniques/Transfection"
    ],
    [
      "plos",
      "/Research and analysis methods/Precipitation techniques/Immunoprecipitation"
    ]
  ],
  "openalex": "W7223857657",
  "pdf_url": "https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1014701&type=printable",
  "pmcid": "PMC13712703",
  "pmid": "42945342",
  "published": "2026-10-27",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/3bybgwfxyvpbr.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:17Z",
      "native_id": "10.1371/journal.ppat.1014701",
      "source": "plos",
      "url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014701"
    },
    {
      "first_seen": "2026-10-31T12:23:13Z",
      "native_id": "PMC13712703",
      "source": "pmc",
      "url": "https://doi.org/10.1371/journal.ppat.1014701"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "plos:gene expression",
      "subfield": "molecular-biology"
    },
    {
      "field": "biology",
      "origin": "heading:Genetics",
      "subfield": "genetics-genomics"
    },
    {
      "field": "biology",
      "origin": "plos:immunology",
      "subfield": "immunology"
    },
    {
      "field": "biology",
      "origin": "plos:microbiology",
      "subfield": "microbiology"
    },
    {
      "field": "medicine",
      "origin": "heading:Medicine and Health Sciences",
      "subfield": "general"
    }
  ],
  "title": "MARK3 promotes host antiviral defense by driving GEF-H1–mediated TBK1 activation",
  "title_text": "MARK3 promotes host antiviral defense by driving GEF-H1–mediated TBK1 activation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:23:13Z",
  "url": "https://research.draconitic.com/paper/3bybgwfxyvpbr",
  "venue": "PLOS Pathogens",
  "versions": []
}