{
  "abstract": "Pathogens deploy effector proteins to exploit host cell biology, and most effector open reading frames (ORFs) are rapidly evolving and lack functional annotation. We developed the effector ORFeome (eORFeome), a scalable functional genomics platform encompassing 3,835 effector ORFs from diverse viruses, bacteria, and parasites. High-throughput barcoded screens across nuclear factor κB (NF-κB), apoptosis, p53, cGAS-STING, and major histocompatibility complex class I (MHC class I) pathways revealed novel pathway-modulating functions for hundreds of uncharacterized eORFs, unexpected activities of known effectors, and distinct pathway-specific functions encoded by single ORFs. Illustrating the power of this approach, we identified HHV6A U14 as a p53 antagonist, HHV7 U21 as a dual-function STING antagonist and MHC-I antigen display inhibitor, and adenoviral 13.6K/i-leader protein as a de novo-evolved TAP inhibitor that suppresses MHC-I display. These results establish a general framework for systematic effector annotation, uncover new mechanisms of host-pathogen interaction across kingdoms, and highlight pathogen effectors as a versatile toolkit for rewiring and probing human cellular pathways.",
  "abstract_shown": true,
  "affiliations": [
    "Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria",
    "Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario",
    "Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Ontario, Canada",
    "Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada",
    "Department of Molecular Genetics, University of Toronto, Ontario, Canada",
    "Centre for Molecular and Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada",
    "Centre for Molecular and Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada",
    "Howard Hughes Medical Institute, Chevy Chase, MD, USA; Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program, New York, NY, USA",
    "Institute of Network Biology (INET), Molecular Targets and Therapeutics Center (MTTC), Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany",
    "Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Centre for Molecular and Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada",
    "Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia",
    "Center for Autoimmune Genomics and Etiology, Division of Allergy & Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA",
    "Center for Autoimmune Genomics and Etiology, Division of Allergy & Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA",
    "Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia",
    "Biology Department and Bioinformatics Program, Boston University, Boston, MA, USA",
    "Center for Autoimmune Genomics and Etiology, Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA",
    "Infection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria, Australia",
    "Center for Autoimmune Genomics and Etiology, Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA",
    "Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada",
    "Infection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, Australia",
    "Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada",
    "Institute of Network Biology (INET), Molecular Targets and Therapeutics Center (MTTC), Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany; Microbe-Host Interactions, Faculty of Biology, Ludwig-Maximilians-Universität (LMU) München, Planegg-Martinsried, Germany",
    "Howard Hughes Medical Institute, Chevy Chase, MD, USA; Laboratory of Membrane Biophysics and Biology, The Rockefeller University, New York, NY, USA",
    "Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria; Medical University of Vienna, Vienna Biocenter (VBC), Vienna, Austria. Electronic address: stark@starklab.org",
    "Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada. Electronic address: mikko.taipale@utoronto.ca"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 25,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Tomás Pachano",
      "orcid": "0000-0003-2823-7715"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "He Leng",
      "orcid": "0009-0003-1558-3341"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Guillaume Dugied",
      "orcid": "0000-0003-0956-2010"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Travis Tribble"
    },
    {
      "affs": [
        0
      ],
      "name": "Vincent Loubière",
      "orcid": "0000-0002-3632-378X"
    },
    {
      "affs": [
        5,
        0
      ],
      "name": "Yeojin Lee"
    },
    {
      "affs": [
        0,
        6
      ],
      "name": "Felix Rauh"
    },
    {
      "affs": [
        7,
        0
      ],
      "name": "Victor Manon"
    },
    {
      "affs": [
        3,
        8
      ],
      "name": "Kevin Yuan"
    },
    {
      "affs": [
        9,
        10
      ],
      "name": "Jocelyn Nurtanto",
      "orcid": "0000-0002-0920-0186"
    },
    {
      "affs": [
        0,
        11
      ],
      "name": "Alexander Schleiffer",
      "orcid": "0000-0001-6251-2747"
    },
    {
      "affs": [
        8,
        12
      ],
      "name": "Veronika Young",
      "orcid": "0000-0002-1524-8039"
    },
    {
      "affs": [
        8,
        12
      ],
      "name": "Benjamin Weller"
    },
    {
      "affs": [
        13,
        14
      ],
      "name": "Eleanor A Lyons",
      "orcid": "0000-0002-0337-7140"
    },
    {
      "affs": [
        15,
        16
      ],
      "name": "Matthew R. Hass",
      "orcid": "0000-0001-9507-4333"
    },
    {
      "affs": [
        17,
        18
      ],
      "name": "Leah Claire Kottyan",
      "orcid": "0000-0003-3979-2220"
    },
    {
      "affs": [
        17,
        8
      ],
      "name": "Matthew T. Weirauch",
      "orcid": "0000-0001-7977-9122"
    },
    {
      "affs": [
        14,
        6
      ],
      "name": "Juan I. Fuxman Bass",
      "orcid": "0000-0001-9457-1207"
    },
    {
      "affs": [
        19,
        0
      ],
      "name": "Hayley J. Newton",
      "orcid": "0000-0002-9240-2001"
    },
    {
      "affs": [
        20,
        2
      ],
      "name": "Alexander W. Ensminger",
      "orcid": "0000-0003-0824-3704"
    },
    {
      "affs": [
        21
      ],
      "name": "Pascal Falter‐Braun",
      "orcid": "0000-0003-2012-6746"
    },
    {
      "affs": [
        22
      ],
      "name": "Jue Chen"
    },
    {
      "affs": [
        9
      ],
      "name": "Daniel Schramek",
      "orcid": "0000-0001-9977-2104"
    },
    {
      "affs": [
        23
      ],
      "name": "Alexander Stark",
      "orcid": "0000-0003-2611-0841"
    },
    {
      "affs": [
        24
      ],
      "name": "Mikko Taipale",
      "orcid": "0000-0003-3811-1761"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2g5y5nqvxzf9m.bib",
  "cited_by": 5,
  "doi": "10.1016/j.cell.2026.06.017",
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  "id": "2g5y5nqvxzf9m",
  "issns": [
    "0092-8674",
    "1097-4172"
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  "landing_url": "https://doi.org/10.1016/j.cell.2026.06.017",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
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  "pdf_url": null,
  "pmcid": "PMC12667889",
  "pmid": "41332698",
  "published": "2026-06-30",
  "publisher": "Cell Press",
  "ris": "https://research.draconitic.com/paper/2g5y5nqvxzf9m.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T13:21:10Z",
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      "url": "https://doi.org/10.1016/j.cell.2026.06.017"
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|interferon and immune responses",
      "subfield": "immunology"
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  "title": "Systematic discovery of pathogen effector functions across human pathogens and pathways",
  "title_text": "Systematic discovery of pathogen effector functions across human pathogens and pathways",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:11Z",
  "url": "https://research.draconitic.com/paper/2g5y5nqvxzf9m",
  "venue": "Cell",
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