{
  "abstract": "Epstein-Barr virus (EBV) is a human herpesvirus that causes a variety of hematological malignancies, in particular B-, T- and NK-cell lymphomas. Latency proteins of the virus contribute to lymphomagenesis by activating the transcription factor NF-κB, however, the molecular mechanism underlying EBV-driven NF-κB activation remains incompletely understood. Here we show that EBV latent membrane proteins LMP1 and LMP2A or LMP2B synergize to activate the protease MALT1, a key driver of NF-κB-mediated lymphocyte proliferation. EBV-positive B-cell lines co-expressing LMP1 and LMP2 proteins exhibited constitutive MALT1 activity, and treatment with a MALT1 inhibitor or silencing of latent membrane protein-1 (LMP1) or LMP2 impaired MALT1-dependent substrate cleavage. LMP1 physically interacted with the MALT1-binding partner BCL10, while LMP2A and LMP2B interacted with MALT1. LMP1 also colocalized with LMP2 in dotted structures, suggesting that LMP1 and LMP2 synergize via the coordinated formation of LMP-BCL10-MALT1 (LBM) complexes. Finally, MALT1 protease inhibition led to reduced expression of a set of NF-κB-driven genes, and reduced tumor growth in an EBV-positive lymphoma xenograft model. These findings establish a key role for the protease MALT1 in LMP1/2-mediated, NF-κB-driven cellular transformation and provide a rationale for inhibiting MALT1 to treat EBV-positive B-cell lymphomas that co-express LMP1 and LMP2.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Immunobiology, University of Lausanne, Epalinges, Switzerland",
    "Institute of Pathology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland",
    "Institute of Microbiology (IMU), Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Mélanie Juilland"
    },
    {
      "affs": [
        0
      ],
      "name": "Laurence Romy",
      "orcid": "0009-0005-3871-7124"
    },
    {
      "affs": [
        0
      ],
      "name": "Harun-Or Rashid"
    },
    {
      "affs": [
        0
      ],
      "name": "Sara Escudeiro Lopes",
      "orcid": "0000-0002-1542-7408"
    },
    {
      "affs": [
        0
      ],
      "name": "Silvia Podavini",
      "orcid": "0009-0001-0704-5506"
    },
    {
      "affs": [
        1
      ],
      "name": "David Vallois",
      "orcid": "0000-0003-0703-6762"
    },
    {
      "affs": [
        0
      ],
      "name": "Manhui Luo"
    },
    {
      "affs": [
        0
      ],
      "name": "Montserrat Gonzalez"
    },
    {
      "affs": [
        0
      ],
      "name": "Katerina Pandeva"
    },
    {
      "affs": [
        0
      ],
      "name": "Frédéric Frête"
    },
    {
      "affs": [
        0
      ],
      "name": "Chantal Décaillet"
    },
    {
      "affs": [
        1
      ],
      "name": "Laurence de Leval",
      "orcid": "0000-0003-3994-516X"
    },
    {
      "affs": [
        2
      ],
      "name": "Sylvia Rothenberger"
    },
    {
      "affs": [
        0
      ],
      "name": "Margot Thome",
      "orcid": "0000-0002-5656-2139"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/83df1pxpbejm5.bib",
  "cited_by": 0,
  "doi": "10.1038/s41375-026-03109-8",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13713546/",
  "id": "83df1pxpbejm5",
  "issns": [
    "0887-6924",
    "1476-5551"
  ],
  "landing_url": "https://doi.org/10.1038/s41375-026-03109-8",
  "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",
      "Article"
    ],
    [
      "openalex",
      "1306|NF-κB Signaling Pathways"
    ]
  ],
  "openalex": "W7202386448",
  "pdf_url": "https://www.nature.com/articles/s41375-026-03109-8.pdf",
  "pmcid": "PMC13713546",
  "pmid": "42595846",
  "published": "2026-08-13",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/83df1pxpbejm5.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:24:04Z",
      "native_id": "PMC13713546",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41375-026-03109-8"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|NF-κB Signaling Pathways",
      "subfield": "oncology"
    }
  ],
  "title": "A role for the protease MALT1 in EBV-mediated B-cell transformation by Latent Membrane Proteins 1 and 2",
  "title_text": "A role for the protease MALT1 in EBV-mediated B-cell transformation by Latent Membrane Proteins 1 and 2",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:21:12Z",
  "url": "https://research.draconitic.com/paper/83df1pxpbejm5",
  "venue": "Leukemia",
  "versions": []
}