{
  "abstract": "The global outbreak of SARS-CoV-2 has resulted in a renewed focus on coronaviruses with the potential for cross-species transmission and mutation risks. In particular, swine acute diarrhea syndrome coronavirus (SADS-CoV), potentially originating from the intermediate horseshoe bat (Rhinolophus affinis), is a novel coronavirus that causes acute diarrhea, vomiting, and high mortality in suckling piglets. Innate immunity plays a crucial role in defending the host against invading pathogens. Previous studies have identified several host factors that inhibit SADS-CoV replication through innate immunity; however, research on SADS-CoV remains insufficient compared to that on other coronaviruses. This study demonstrates that Moloney leukemia virus 10 protein (MOV10) exerts anti-SADS-CoV activity via its N-terminal domain in a helicase activity-independent manner. Mechanistic analysis reveals that MOV10 induces translocation of tripartite motif-containing 24 (TRIM24) from the nucleus to the cytoplasm. The cytoplasmically localized TRIM24 binds to MOV10 and TNF receptor-associated factor 3 (TRAF3) to form a ternary complex. Functional studies demonstrate that MOV10 strengthens the interaction between TRIM24 and TRAF3 in a dose-dependent manner and facilitates TRIM24-mediated K63-linked ubiquitination of TRAF3, thereby activating interferon immune responses. Furthermore, we identify the strategies by which SADS-CoV evades innate immunity. The viral N protein inhibits the antiviral effect of MOV10 by disrupting the interaction between MOV10 and TRAF3 and by promoting K48-linked polyubiquitination of TRAF3, leading to TRAF3 degradation via the ubiquitin-proteasome pathway. Collectively, our findings reveal the role of MOV10 in antiviral immunity and how SADS-CoV evades host immune defense.\n\nIMPORTANCE: Moloney leukemia virus 10 protein (MOV10), a DExD-box RNA helicase, is a known component of cytoplasmic RNA processing centers known as P bodies. As an interferon-stimulated gene (ISG), MOV10 exhibits broad-spectrum antiviral activity against multiple viruses, including SARS-CoV-2, HIV, HSV-1, IAV, and PRRSV. Here, we identify a novel helicase-independent antiviral mechanism of MOV10 against SADS-CoV. In this study, we show that MOV10 bridges TRIM24 and TRAF3 and facilitates K63-linked ubiquitination of TRAF3 independent of its helicase activity. This process strongly amplifies downstream interferon antiviral responses and suppresses viral replication. Furthermore, the SADS-CoV N protein efficiently antagonizes MOV10-mediated immune defense by disrupting the MOV10-TRAF3 interaction and inducing K48-linked ubiquitination and proteasomal degradation of TRAF3. Collectively, this study establishes a previously uncharacterized MOV10-TRIM24-TRAF3 antiviral regulatory axis, which offers new mechanistic insights into how coronaviruses evade host immune defenses.",
  "abstract_shown": true,
  "affiliations": [
    "State Key Laboratory of Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Miaomiao Zeng"
    },
    {
      "affs": [
        0
      ],
      "name": "Dakai Liu",
      "orcid": "0009-0000-7607-6018"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiyu Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Liaoyuan Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Hongyan Shi"
    },
    {
      "affs": [
        0
      ],
      "name": "Xin Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jianfei Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiuwen Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Jialin Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Tingshuai Feng"
    },
    {
      "affs": [
        0
      ],
      "name": "Xinwei Sun"
    },
    {
      "affs": [
        0
      ],
      "name": "Junyi Su"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhaoyang Ji"
    },
    {
      "affs": [
        0
      ],
      "name": "Li Feng",
      "orcid": "0000-0003-4123-0892"
    },
    {
      "affs": [
        0
      ],
      "name": "Da Shi",
      "orcid": "0000-0002-1386-775X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a7pmshfc1bt08.bib",
  "cited_by": 0,
  "doi": "10.1128/jvi.01215-26",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13712983/",
  "id": "a7pmshfc1bt08",
  "issns": [
    "0022-538X",
    "1098-5514"
  ],
  "landing_url": "https://doi.org/10.1128/jvi.01215-26",
  "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",
      "Virus-Cell Interactions"
    ],
    [
      "openalex",
      "2403|interferon and immune responses"
    ]
  ],
  "openalex": "W7121614956",
  "pdf_url": null,
  "pmcid": "PMC13712983",
  "pmid": "42808732",
  "published": "2026-09-29",
  "publisher": "American Society for Microbiology (ASM)",
  "ris": "https://research.draconitic.com/paper/a7pmshfc1bt08.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:23:27Z",
      "native_id": "PMC13712983",
      "source": "pmc",
      "url": "https://doi.org/10.1128/jvi.01215-26"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|interferon and immune responses",
      "subfield": "immunology"
    }
  ],
  "title": "MOV10 inhibits SADS-CoV replication by enhancing TRIM24-mediated K63-linked TRAF3 ubiquitination, and this inhibition is antagonized by viral N protein",
  "title_text": "MOV10 inhibits SADS-CoV replication by enhancing TRIM24-mediated K63-linked TRAF3 ubiquitination, and this inhibition is antagonized by viral N protein",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:23:27Z",
  "url": "https://research.draconitic.com/paper/a7pmshfc1bt08",
  "venue": "Journal of Virology",
  "versions": []
}