{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:31:23Z","timestamp":1787016683717,"version":"build-2736575974"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473330"],"award-info":[{"award-number":["82473330"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32200124"],"award-info":[{"award-number":["32200124"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20210901"],"award-info":[{"award-number":["BK20210901"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2025,7,22]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Oncolytic adenoviruses (OAVs) engineered to carry antitumor or immune-activating transgenes are being actively explored for cancer immunotherapy. While many efforts have focused on modifying OAVs to counteract the immunosuppressive tumor microenvironment, comparatively less attention has been given to enhancing OAV replication by targeting host factors to increase oncolytic activity. Here, we report that TRIM56 is strongly upregulated during HAdV-C5 infection, with its expression correlating with increasing levels of the viral E1A protein, ultimately promoting HAdV-C5 replication. Mechanistically, TRIM56 stabilizes the viral E1A protein and enhances viral genome transcription. To leverage this effect, we engineered a recombinant oncolytic adenovirus expressing TRIM56 (OAV-TRIM56) and found that it achieved significantly higher replication titers\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      compared to conventional OAVs, leading to superior antitumor efficacy\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      . Our study presents a novel strategy to enhance OAV replication by targeting host factors, offering a promising approach for improving oncolytic virotherapy.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>Adenoviruses (Ads) can be engineered into replication-defective adenoviral (Adv) vectors and replication-competent oncolytic adenovirus (OAd), both of which are widely used in gene therapy and virotherapy. Understanding the mechanisms regulating adenoviral infection is crucial for optimizing the therapeutic potential of Adv and OAd. In this study, we demonstrate for the first time that TRIM56, a host protein broadly expressed in various cell types, stabilizes the adenoviral E1A protein and assists E1A in antagonizing STING, thereby significantly enhancing adenoviral replication. Our findings provide new insights into strategies for improving the efficacy of Adv and OAd in gene therapy.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00041-25","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T09:00:35Z","timestamp":1748941235000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["TRIM56 enhances adenoviral E1A steady state to improve oncolytic adenovirus therapy efficacy"],"prefix":"10.1128","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5142-227X","authenticated-orcid":true,"given":"Nan","family":"Sun","sequence":"first","affiliation":[{"name":"Cancer Institute, Xuzhou Medical University","place":["Xuzhou, China"]},{"name":"Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University","place":["Xuzhou, China"]},{"name":"Jiangsu Center for the Collaboration and 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