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oai:figshare.com:article/33971320 2026-09-23T06:03:34Z category_8 portal_316 item_type_3 month_year_09_2026

Supplementary file 1_Biological characterization of a clinical human adenovirus type 3 isolate with oncolytic potential.docx Zhiwei Shen (562324) Rui Tian (635672) Tianhao Wu (641064) Xiaojing Ou (25094689) Jiaqi Zhang (412762) Zhiyuan Li (205620) Meiyuan Gong (11936162) Meng Meng (462502) Luyao Ji (25094692) Zhenyu Rong (25094695) Yaxuan Sun (2165998) Xuyue Zhang (25094698) Zeyang Tang (25094701) Yue Li (102191) Wenqing Yu (5759768) Feng Han (10919) Yonglin Yang (8135928) Wenlong Dai (20784257) Microbiology apoptosis clinical isolate human adenovirus type 3 oncolytic virotherapy viral tropism Introduction<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.</p>Methods<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.</p>Results<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.</p>Conclusion<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.</p> 2026-09-23T06:03:34Z Dataset Dataset 10.3389/fmicb.2026.1912909.s001 https://figshare.com/articles/dataset/Supplementary_file_1_Biological_characterization_of_a_clinical_human_adenovirus_type_3_isolate_with_oncolytic_potential_docx/33971320 CC BY 4.0