{
  "abstract": "Protein phosphatase 1 regulatory subunit 3G (PPP1R3G) is one of the regulatory subunits of protein phosphatase 1 (PP1). Current research on PPP1R3G is primarily focused on glycogen synthesis and lipid metabolism. However, the role of ppp1r3g in the innate immune response of fish has not been completely elucidated. This study demonstrated that ppp1r3g regulates RLR signaling pathway through interactions with Rig-I, Mda5, and Traf6. In parallel, Ppp1r3g inhibits platelet activation by regulating 14-3-3 zeta (14-3-3ζ) and consequently modulating the formation of the 14-3-3ζ-integrin-β3 (Itgb3) complex. In vivo analysis revealed that compared with the wild-type controls, ppp1r3g-null rare minnow (Gobiocypris rarus) and ppp1r3g-chimera grass carp (Ctenopharyngodon idella) exhibited significantly enhanced resistance to grass carp reovirus (GCRV), with markedly alleviated hemorrhagic symptoms post-infection. Furthermore, knockdown of ppp1r3g suppressed GCRV replication and upregulated type I interferon (IFN-1) expression in grass carp kidney (CIK) cells. Additionally, Ppp1r3g binds to the -ESKVFYLKMKGDYYRYL- fragment (EL17) of 14-3-3ζ via the Ser36/37 phosphorylation site located on the PP1c domain. This study also demonstrated that 14-3-3ζ interacts with Itgb3 through this fragment, indicating that Ppp1r3g competes with Itgb3 to bind 14-3-3ζ. Furthermore, Ppp1r3g dose-dependently promoted Itgb3 degradation via a proteolytic pathway. These findings indicate that Ppp1r3g negatively regulates innate antiviral immunity after GCRV stimulation and suppresses platelet and coagulation cascade activation by modulating the interaction between 14-3-3ζ and Itgb3 in fish. Author summary: Grass carp reovirus (GCRV) infection is associated with high lethality in grass carp and rare minnow. The primary symptom of GCRV is massive hemorrhaging in various tissues (hemorrhagic disease). Therefore, alleviating hemorrhagic symptoms is considered important for improving survival following GCRV infection. This study demonstrated that GCRV promotes ppp1r3g induction, suppressing the activation of the fish innate immune system by negatively regulating RLR signaling. Furthermore, Ppp1r3g competes with integrin-β3 (Itgb3) for binding to 14-3-3ζ and promotes Itgb3 degradation in a proteasome-dependent manner, which inhibits the formation of the 14-3-3ζ-Itgb3 complex, suppressing platelet activation. Thus, this study revealed the role of Ppp1r3g in fish innate immunity and elucidated its regulatory mechanism in the coagulation pathway.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China",
    "University of Chinese Academy of Sciences, Beijing, China",
    "Fisheries College, Hunan Agricultural University, Changsha, China"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ruyi Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Man Zhou"
    },
    {
      "affs": [
        2
      ],
      "name": "Yuxuan Wang"
    },
    {
      "name": "Xudong Hu"
    },
    {
      "name": "Han Zhang"
    },
    {
      "name": "Hong Cao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bftbpwww68txm.bib",
  "cited_by": 1,
  "doi": "10.1371/journal.ppat.1014590",
  "fulltext_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014590",
  "id": "bftbpwww68txm",
  "issns": [
    "1553-7374"
  ],
  "landing_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014590",
  "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",
      "2403|Aquaculture disease management and microbiota"
    ],
    [
      "plos",
      "/Biology and life sciences/Developmental biology/Life cycles/Larvae"
    ],
    [
      "plos",
      "/Biology and life sciences/Immunology/Immune response/Antiviral immune response"
    ],
    [
      "plos",
      "/Biology and life sciences/Molecular biology/Molecular biology techniques/Molecular probe techniques/Immunoblotting"
    ],
    [
      "plos",
      "/Biology and life sciences/Molecular biology/Molecular biology techniques/Transfection"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Eukaryota/Animals/Vertebrates/Fish/Osteichthyes/Carps"
    ],
    [
      "plos",
      "/Biology and life sciences/Zoology/Animals/Vertebrates/Fish/Osteichthyes/Carps"
    ],
    [
      "plos",
      "/Medicine and health sciences/Clinical medicine/Signs and symptoms/Hemorrhage"
    ],
    [
      "plos",
      "/Medicine and health sciences/Hematology/Blood coagulation/Platelet activation"
    ],
    [
      "plos",
      "/Medicine and health sciences/Immunology/Immune response/Antiviral immune response"
    ],
    [
      "plos",
      "/Medicine and health sciences/Vascular medicine/Hemorrhage"
    ],
    [
      "plos",
      "/Research and analysis methods/Molecular biology techniques/Molecular probe techniques/Immunoblotting"
    ],
    [
      "plos",
      "/Research and analysis methods/Molecular biology techniques/Transfection"
    ],
    [
      "plos",
      "/Research and analysis methods/Precipitation techniques/Immunoprecipitation"
    ]
  ],
  "openalex": "W7213557939",
  "pdf_url": "https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1014590&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-18",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/bftbpwww68txm.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:49Z",
      "native_id": "10.1371/journal.ppat.1014590",
      "source": "plos",
      "url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014590"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "plos:molecular biology",
      "subfield": "molecular-biology"
    },
    {
      "field": "biology",
      "origin": "plos:developmental biology",
      "subfield": "developmental-biology"
    },
    {
      "field": "biology",
      "origin": "plos:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Grass carp reovirus activates fish Ppp1r3g to suppress innate immunity and exacerbate hemorrhage via the 14-3-3ζ/Itgb3 signaling axis",
  "title_text": "Grass carp reovirus activates fish Ppp1r3g to suppress innate immunity and exacerbate hemorrhage via the 14-3-3ζ/Itgb3 signaling axis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:49Z",
  "url": "https://research.draconitic.com/paper/bftbpwww68txm",
  "venue": "PLOS Pathogens",
  "versions": []
}