{
  "abstract": "Tonate virus (TONV) is a neglected mosquito-borne alphavirus of the Venezuelan equine encephalitis complex associated with febrile illness, encephalitis, and fetal central nervous system abnormalities. Yet, host pathways that sense TONV infection and restrict its replication remain poorly defined. Here, we investigated the interaction between TONV and the type I interferon (IFN-I) system in human T98G and A549 cells. We show that TONV infection led to the accumulation of cytosolic double-stranded RNA and a robust IFN response. RIG-I and MDA5 depletion as well as that of MAVS and IRF3 strongly reduced TONV-induced IFN response. Disruption of RIG-I, MDA5, MAVS, or IRF3 resulted in an increase of dsRNA-positive cells and a higher viral RNA accumulation. Finally, we found that treatment with exogenous IFN-I strongly inhibits TONV replication, reducing both viral RNA loads and infectious particle production. Thus, together, our results identify the RIG-I/MDA5-MAVS-IRF3 axis as a major pathway sensing TONV infection and establishing an IFN-I-dependent antiviral state, providing the first molecular characterization of TONV innate immune sensing in human cells. Author summary: Tonate virus is an understudied mosquito-borne virus that circulates in South America. Most recognized human infections resemble other mosquito-borne febrile illnesses, which may contribute to underdiagnosis, although severe cases including brain inflammation and fetal abnormalities have been reported. We investigated how human cells detect Tonate virus and mount an antiviral response. We found that infection activates key cellular sensors that signal through a common pathway to induce type I interferons. Disrupting components of this pathway reduced interferon production and allowed greater accumulation of viral RNA, demonstrating that this pathway contributes directly to controlling Tonate virus infection. Conversely, treating cells with type I interferon prior to infection strongly reduced viral replication and production of infectious particles. Together, our findings provide the first molecular description of how human cells sense and restrict Tonate virus. Our study provides a foundation for future work on Tonate virus pathogenesis, immune control, and potential antiviral interventions.",
  "abstract_shown": true,
  "affiliations": [
    "Institut de Génétique Moléculaire de Montpellier (IGMM), Univ Montpellier, CNRS, Montpellier, France",
    "MIVEGEC, Univ Montpellier, CNRS, IRD, Montpellier, France",
    "Department of Medical Technology, LMI PRESTO, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Thomas Labadie",
      "orcid": "0000-0001-5263-3895"
    },
    {
      "affs": [
        0
      ],
      "name": "Roger Eloiflin",
      "orcid": "0000-0001-5927-5592"
    },
    {
      "affs": [
        0
      ],
      "name": "Zoé Denis"
    },
    {
      "affs": [
        1
      ],
      "name": "Marie Motos"
    },
    {
      "affs": [
        0
      ],
      "name": "Joanna Re"
    },
    {
      "affs": [
        0
      ],
      "name": "Moritz Schüssler",
      "orcid": "0000-0002-2298-3963"
    },
    {
      "affs": [
        0
      ],
      "name": "Morgane Chemarin"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Isabelle Moltini-Conclois"
    },
    {
      "affs": [
        0
      ],
      "name": "Valérie Courgnaud"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Dorothée Missé"
    },
    {
      "affs": [
        0
      ],
      "name": "Nadine Laguette",
      "orcid": "0000-0001-8072-5607"
    },
    {
      "affs": [
        0
      ],
      "name": "Karim Majzoub",
      "orcid": "0000-0001-7345-6840"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0wk7jbjb9cd3n.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pntd.0014559",
  "fulltext_url": "https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014559",
  "id": "0wk7jbjb9cd3n",
  "issns": [
    "1935-2735",
    "1935-2727"
  ],
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  "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",
      "Alphaviruses"
    ],
    [
      "heading",
      "Biochemistry"
    ],
    [
      "heading",
      "Biology and Life Sciences"
    ],
    [
      "heading",
      "Biology and life sciences"
    ],
    [
      "heading",
      "Cognitive Psychology"
    ],
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      "heading",
      "Cognitive Science"
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      "heading",
      "Cytokines"
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      "Double stranded RNA"
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      "Guide RNA"
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      "heading",
      "Medicine and Health Sciences"
    ],
    [
      "heading",
      "Microbial Pathogens"
    ],
    [
      "heading",
      "Microbiology"
    ],
    [
      "heading",
      "Molecular Development"
    ],
    [
      "heading",
      "Neuroscience"
    ],
    [
      "heading",
      "Nucleic acids"
    ],
    [
      "heading",
      "Organisms"
    ],
    [
      "heading",
      "Pathogens"
    ],
    [
      "heading",
      "Pathology and Laboratory Medicine"
    ],
    [
      "heading",
      "Perception"
    ],
    [
      "heading",
      "Physiology"
    ],
    [
      "heading",
      "Proteins"
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    [
      "heading",
      "Psychology"
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    [
      "heading",
      "RNA"
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    [
      "heading",
      "RNA viruses"
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      "heading",
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    ],
    [
      "heading",
      "Sensory Perception"
    ],
    [
      "heading",
      "Social Sciences"
    ],
    [
      "heading",
      "Togaviruses"
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    [
      "heading",
      "Tonate Virus"
    ],
    [
      "heading",
      "Viral Pathogens"
    ],
    [
      "heading",
      "Viral Replication"
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    [
      "heading",
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    ],
    [
      "heading",
      "Viruses"
    ],
    [
      "openalex",
      "2403|interferon and immune responses"
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      "plos",
      "/Biology and life sciences/Biochemistry/Nucleic acids/RNA/Double stranded RNA"
    ],
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      "plos",
      "/Biology and life sciences/Biochemistry/Nucleic acids/RNA/Guide RNA"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Interferons"
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      "/Biology and life sciences/Developmental biology/Molecular development/Cytokines"
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      "plos",
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      "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Viral pathogens/Togaviruses/Alphaviruses/Tonate virus"
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    [
      "plos",
      "/Biology and life sciences/Microbiology/Virology/Viral replication"
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    [
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    [
      "plos",
      "/Biology and life sciences/Organisms/Viruses/Viral pathogens/Togaviruses/Alphaviruses"
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    [
      "plos",
      "/Biology and life sciences/Organisms/Viruses/Viral pathogens/Togaviruses/Alphaviruses/Tonate virus"
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    [
      "plos",
      "/Biology and life sciences/Physiology/Immune physiology/Cytokines"
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      "plos",
      "/Biology and life sciences/Psychology/Cognitive psychology/Perception/Sensory perception"
    ],
    [
      "plos",
      "/Medicine and health sciences/Immunology/Immune system/Innate immune system/Cytokines"
    ],
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      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Viral pathogens/Togaviruses/Alphaviruses"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Viral pathogens/Togaviruses/Alphaviruses/Tonate virus"
    ],
    [
      "plos",
      "/Social sciences/Psychology/Cognitive psychology/Perception/Sensory perception"
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  ],
  "openalex": "W7222615512",
  "pdf_url": "https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0014559&type=printable",
  "pmcid": "PMC13712696",
  "pmid": "42886769",
  "published": "2026-10-16",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/0wk7jbjb9cd3n.ris",
  "sources": [
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      "first_seen": "2026-10-30T12:17:23Z",
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      "source": "plos",
      "url": "https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014559"
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    {
      "first_seen": "2026-10-31T12:23:13Z",
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      "url": "https://doi.org/10.1371/journal.pntd.0014559"
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "heading:Biochemistry",
      "subfield": "general"
    },
    {
      "field": "biology",
      "origin": "heading:Developmental Biology",
      "subfield": "developmental-biology"
    },
    {
      "field": "biology",
      "origin": "plos:immunology",
      "subfield": "immunology"
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    {
      "field": "biology",
      "origin": "plos:microbiology",
      "subfield": "microbiology"
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    {
      "field": "biology",
      "origin": "plos:neuroscience",
      "subfield": "neuroscience"
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  ],
  "title": "The RLR-MAVS-IRF3 axis activates the IFN pathway to restrict Tonate virus infection",
  "title_text": "The RLR-MAVS-IRF3 axis activates the IFN pathway to restrict Tonate virus infection",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:23:13Z",
  "url": "https://research.draconitic.com/paper/0wk7jbjb9cd3n",
  "venue": "PLOS Neglected Tropical Diseases",
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}