ArticleCell genomics2026
Systematic investigation reveals extensive Epstein-Barr virus transcriptional regulation of the human genome.
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Article in Cell genomics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Systematic mapping of chromatin dysregulation driven by viral transcriptional regulators at scale.bioRxiv : the preprint server for biology · 2026Article
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Authors and funding
22 authors.
Phillip J DexheimerCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Matthew R HassCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Lee E EdsallCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Arame A DioufCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Sydney H JonesCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Omer DonmezCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Cailing YinCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Katelyn A DunnCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Carmy ForneyCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Hayley K HesseCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Andrew VonHandorfCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Xiaoting ChenCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Sreeja ParameswaranCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Olivia E GittensCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Kenyatta C M F VielCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Rozita RazaviDepartment of Molecular Genetics, University of Toronto, Toronto, ON M5S 3G9, Canada; Donnelly Centre, University of Toronto, Toronto, ON M5S 3G9, Canada.
Benjamin E GewurzDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Bo ZhaoDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Lucinda P LawsonCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Timothy R HughesDepartment of Molecular Genetics, University of Toronto, Toronto, ON M5S 3G9, Canada; Donnelly Centre, University of Toronto, Toronto, ON M5S 3G9, Canada.
Leah C KottyanCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA. Electronic address: leah.kottyan@cchmc.org.
Matthew T WeirauchCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA; Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. Electronic address: matthew.weirauch@cchmc.org.
Funding
TSLP, IL-9-producing mucosal mast cells, and allergic inflammationU19AI070235 · NIAID · CINCINNATI CHILDRENS HOSP MED CTR · PI Gurjit K. Khurana Hershey · 2006 to 2026
$31.3MResearch Project 3: Role of Posttranslational Protein Modifications in the Pathogenesis of Ebola Virus DiseaseP01AI150585 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI BUKREYEV, ALEXANDER · 2021 to 2025
$11.3MHLA GENE COMPLEMENTATION IN PRIMARY SJOGREN'S AND LUPUSR01AI024717 · NIAID · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI KOTTYAN, LEAH CLAIRE, WEIRAUCH, MATTHEW TYSON · 1987 to 2025
$7.8MTissue Repository CoreP30AR070549 · NIAMS · CINCINNATI CHILDRENS HOSP MED CTR · PI Leah Claire Kottyan · 2016 to 2026
$7.7MPolygenic Risk Scores for Healthier African American FamiliesU01HG011172 · NHGRI · CINCINNATI CHILDRENS HOSP MED CTR · PI Leah Claire Kottyan, LISA J MARTIN · 2020 to 2026
$7.2MGene Regulation as a Foundation for Autoimmune Disease PreventionU01AI130830 · NIAID · CINCINNATI CHILDRENS HOSP MED CTR · PI WEIRAUCH, MATTHEW TYSON · 2017 to 2021
$7.2MBinding of Epstein Barr Virus EBNA2 Unifies Multiple Sclerosis Genetic MechanismsR01NS099068 · NINDS · CINCINNATI CHILDRENS HOSP MED CTR · PI Leah Claire Kottyan, Matthew Tyson Weirauch · 2017 to 2026
$4.2MGenomics of Inflammatory Bowel DiseaseR01AI148276 · NIAID · CINCINNATI CHILDRENS HOSP MED CTR · PI KOTTYAN, LEAH CLAIRE · 2019 to 2023
$3.9MRegulation of the Epstein-Barr Virus Lytic SwitchR01AI164709 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI Benjamin Elison Gewurz · 2021 to 2026
$3.1MVirus-driven human gene misregulation in diseaseR01HG010730 · NHGRI · CINCINNATI CHILDRENS HOSP MED CTR · PI WEIRAUCH, MATTHEW TYSON · 2020 to 2023
$2.7MTranscription Factor Genetics in LupusR01AR073228 · NIAMS · CINCINNATI CHILDRENS HOSP MED CTR · PI KOTTYAN, LEAH CLAIRE, WAGGONER, STEPHEN N. · 2019 to 2023
$2.2MCINCINNATI TRAINING PROGRAM IN PEDIATRIC RHEUMATOLOGYRESEARCHT32AR069512 · NIAMS · CINCINNATI CHILDRENS HOSP MED CTR · PI ALEXEI A GROM, Grant Sanford Schulert · 2016 to 2026
$1.6MNHGRI NIH HHS R01 HG010730NHGRI NIH HHS U01 HG011172NHGRI NIH HHS U24 HG013078NIAID NIH HHS P01 AI150585NIAID NIH HHS R01 AI024717NIAID NIH HHS R01 AI148276NIAID NIH HHS R01 AI164709NIAID NIH HHS U01 AI130830NIAID NIH HHS U19 AI070235NIAMS NIH HHS P30 AR070549NIAMS NIH HHS R01 AR073228NIAMS NIH HHS T32 AR069512NIDCR NIH HHS R01 DE033907NINDS NIH HHS R01 NS099068
Abstract
We systematically investigate interactions between Epstein-Barr virus (EBV) transcriptional regulators (viral transcriptional regulators [vTRs]) and the human genome. Starting with 16 known and candidate vTRs, we identify nine whose introduction into human cells results in substantial alterations to host gene expression. Genome-scale profiling of vTR binding, chromatin accessibility alterations, and gene expression impact reveals extensive EBV functional interactions with the human genome, including >100,000 vTR binding events impacting almost a quarter of human genes. BMRF1 emerges as a potent regulator, impacting >7,000 genes and altering >37,000 chromatin regions. Our results reveal that EBV RTA interacts with and stabilizes the binding of human RBPJ. Network analysis reveals that many human genes are targeted by multiple EBV-vTRs, highlighting the vast coordinated impact of EBV on human gene expression. This study provides a valuable, extensive resource for examining EBV-induced alterations to human gene regulation, with data available on multiple platforms.
Indexed as
Genome, HumanHerpesvirus 4, HumanChromatinEpstein-Barr Virus InfectionsGene Expression RegulationGene Expression Regulation, ViralHumansImmediate-Early ProteinsImmunoglobulin J Recombination Signal Sequence-Binding ProteinTrans-ActivatorsTranscription, GeneticBRLF1 protein, Human herpesvirus 4ChromatinImmediate-Early ProteinsImmunoglobulin J Recombination Signal Sequence-Binding ProteinRBPJ protein, humanTrans-ActivatorsEBVEpstein-Barr virusfunctional genomicsregulatory networkssystems biologytranscriptional regulationvirologyvirus-host interactions
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.