{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T07:01:16Z","timestamp":1790146876684,"version":"4.0.1"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Human adenovirus type 3 (HAdV-3) is a major adenovirus type associated with respiratory infections in China. Despite its clinical importance, the biological characteristics and potential biomedical applications of contemporary circulating HAdV-3 strains remain incompletely understood. Naturally occurring species B adenoviruses also remain relatively underexplored as potential starting backbones for oncolytic virotherapy. This study aimed to characterize a contemporary clinical HAdV-3 isolate and evaluate its viral genome amplification, apoptosis induction, and antitumor activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A clinical HAdV-3 isolate, designated HAdV-3-TZ01, was recovered from a throat swab specimen from a patient with adenovirus-associated respiratory disease. Viral identity and genomic characteristics were determined using multiplex PCR, Sanger sequencing, whole-genome sequencing, phylogenetic analysis, and recombination analysis. Viral genome amplification kinetics were evaluated in human respiratory-related and tumor-derived cell lines and a murine cell line by quantitative PCR. Comparative apoptosis induction by HAdV-3-TZ01 and HAdV-5 was assessed in 293F cells infected at a low multiplicity of infection using Annexin V\/PI flow cytometry. Antitumor activity was evaluated following repeated intratumoral administration of HAdV-3-TZ01 in an A549-luciferase xenograft model in BALB\/c-nu nude mice, with tumor growth and bioluminescence monitored longitudinally.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Genomic and phylogenetic analyses confirmed that HAdV-3-TZ01 belonged to HAdV-3 within species B and exhibited a genomic backbone highly conserved with contemporary circulating HAdV-3 strains. A short putative HAdV-7-derived recombinant fragment was identified. HAdV-3-TZ01 showed efficient viral genome amplification in multiple human respiratory-related cell lines, including A549, H3122, BEAS-2B, MRC-5, and HEK293FT cells, whereas genome amplification was markedly restricted in murine L929 cells. HAdV-3-TZ01 induced a significantly higher proportion of late apoptotic cells than HAdV-5 in 293F cells under low-multiplicity infection conditions, although the absolute increase in total apoptosis was modest. In the A549-luciferase xenograft model, intratumoral administration of HAdV-3-TZ01 significantly suppressed tumor progression. By day 43, mean tumor volume was reduced by approximately 54% and tumor-associated bioluminescence by approximately 50% compared with mock-treated controls. No significant body-weight loss or overt signs of distress were observed under the experimental conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>HAdV-3-TZ01 retains the characteristic human epithelial tropism of HAdV-3 and exhibits efficient viral genome amplification in human epithelial-derived cells, apoptosis induction, and measurable antitumor activity in vivo. The apoptosis difference between HAdV-3-TZ01 and HAdV-5 should be interpreted cautiously because the analysis was limited to 293F cells and did not establish a tumor-specific pro-apoptotic mechanism. As an unmodified respiratory pathogen, HAdV-3-TZ01 should not be considered a directly translatable therapeutic agent. Rather, these findings support HAdV-3-TZ01 as a potential starting backbone for future genetic engineering aimed at improving tumor selectivity and safety.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1912909","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:16:33Z","timestamp":1790144193000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Biological characterization of a clinical human adenovirus type 3 isolate with oncolytic potential"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhiwei","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, National Vaccine Innovation Platform, School of Pharmacy, Nanjing Medical University","place":["Nanjing, China"]},{"name":"Nanjing Medical University Taizhou Institute of Pharmaceutical Industry","place":["Taizhou, 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Ou","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, National Vaccine Innovation Platform, School of Pharmacy, Nanjing Medical University","place":["Nanjing, China"]},{"name":"Nanjing Medical University Taizhou Institute of Pharmaceutical Industry","place":["Taizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, National Vaccine Innovation Platform, School of Pharmacy, Nanjing Medical University","place":["Nanjing, China"]},{"name":"Nanjing Medical University Taizhou Institute of Pharmaceutical Industry","place":["Taizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, National Vaccine Innovation Platform, School of Pharmacy, Nanjing Medical University","place":["Nanjing, China"]},{"name":"Nanjing Medical University Taizhou Institute of Pharmaceutical Industry","place":["Taizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiyuan","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, National Vaccine Innovation Platform, School of Pharmacy, Nanjing Medical University","place":["Nanjing, China"]},{"name":"Nanjing Medical University Taizhou Institute of Pharmaceutical Industry","place":["Taizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, National Vaccine Innovation Platform, School of Pharmacy, Nanjing Medical University","place":["Nanjing, China"]},{"name":"Nanjing Medical University Taizhou Institute of Pharmaceutical Industry","place":["Taizhou, 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Pharmacy, Nanjing Medical University","place":["Nanjing, China"]},{"name":"Nanjing Medical University Taizhou Institute of Pharmaceutical Industry","place":["Taizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, National Vaccine Innovation Platform, School of Pharmacy, Nanjing Medical University","place":["Nanjing, China"]},{"name":"Nanjing Medical University Taizhou Institute of Pharmaceutical Industry","place":["Taizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyang","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, National Vaccine Innovation Platform, School of Pharmacy, Nanjing Medical University","place":["Nanjing, China"]},{"name":"Nanjing Medical University Taizhou Institute of Pharmaceutical Industry","place":["Taizhou, 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Brain-Inspired Intelligence Technology","place":["Nanjing, China"]},{"name":"Research Center for Pharmaceutical Synthetic Biology, School of Pharmacy, Nanjing Medical University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonglin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Institute of Hepatology, Taizhou School of Clinical Medicine Nanjing Medical University, The Affiliated Taizhou People's Hospital of Nanjing Medical University","place":["Taizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlong","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, National Vaccine Innovation Platform, School of Pharmacy, Nanjing Medical University","place":["Nanjing, China"]},{"name":"Nanjing Medical University Taizhou Institute of Pharmaceutical Industry","place":["Taizhou, China"]},{"name":"Research Center for Pharmaceutical 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