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However, the role of EBV co-infection in\n                      <jats:italic toggle=\"yes\">H. pylori<\/jats:italic>\n                      -related cancers remains unclear because of the lack of efficient\n                      <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                      models. Organoids, which are derived from self-renewing stem cells, closely mimic\n                      <jats:italic toggle=\"yes\">in situ<\/jats:italic>\n                      tissue structure and function, making them ideal for disease modeling. Here, we developed patient-derived normal gastric organoids (NGOs) and used high-accuracy microinjection to introduce EBV and\n                      <jats:italic toggle=\"yes\">H. pylori<\/jats:italic>\n                      (NCTC11637 strain). We found that the co-infection of\n                      <jats:italic toggle=\"yes\">H. pylori<\/jats:italic>\n                      and EBV induced a significant structural change and upregulated the expression of\n                      <jats:italic toggle=\"yes\">TFF1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">VIL1<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">Lgr5<\/jats:italic>\n                      to promote cell proliferation and tissue morphogenesis. Analysis of transmission electron microscopy revealed an increase of\n                      <jats:italic toggle=\"yes\">H. pylori<\/jats:italic>\n                      internal location in NGOs after co-infection. Moreover, all tested\n                      <jats:italic toggle=\"yes\">H. pylori<\/jats:italic>\n                      strains isolated from patients displayed similar toxicities when co-infected with EBV. These findings provide a fundamental basis for evaluating pathogen toxicity, predicting disease progression, and advancing the clinical treatment of gastric cancer.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Helicobacter pylori<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">H. pylori<\/jats:italic>\n                      ) infection is a major contributor to chronic inflammation and the development of gastric cancer. Furthermore, Epstein-Barr virus (EBV) has been shown to play a role in the oncogenic process of gastric cancer by promoting chronic inflammation and increasing tissue damage. However, the mechanism by which co-infection contributes to gastric carcinogenesis remains unclear. In this study, we used patient-derived gastric organoids as a model to establish EBV-\n                      <jats:italic toggle=\"yes\">H. pylori<\/jats:italic>\n                      co-infection using microinjection technology and found that co-infection causes significant structural changes and promotes cell proliferation. This model will not only contribute to a better understanding of the pathogenesis of gastric cancer but will also be important for drug efficacy evaluation and the development of new therapeutic approaches.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00928-25","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T13:00:35Z","timestamp":1755694835000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["Co-infection of\n                    <i>Helicobacter pylori<\/i>\n                    with Epstein-Barr virus in gastric organoids enhances cell proliferation and 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