title: Adenovirus with DNA Packaging Gene Mutations Increased Virus Release.
abstract: Adenoviruses (Ads) have been extensively manipulated for the development of cancer selective replication, leading to cancer cell death or oncolysis. Clinical studies usingE1-modified oncolytic Ads have shown that this therapeutic platform was safe, but with limited efficacy, indicating the necessity of targeting other viral genes for manipulation. To improve the therapeutic efficacy of oncolytic Ads, we treated the entire Ad genome repeatedly with UV-light and have isolated AdUV which efficiently lyses cancer cells as reported previously (Wechman, S. L. et al. Development of an Oncolytic Adenovirus with Enhanced Spread Ability through Repeated UV Irradiation and Cancer Selection.Viruses2016,8, 6). In this report, we show that no mutations were observed in the early genes (E1orE4) of AdUV while several mutations were observed within the Ad late genes which have structural or viral DNA packaging functions. This study also reported the increased release of AdUV from cancer cells. In this study, we found that AdUV inhibits tumor growth following intratumoral injection. These results indicate the potentially significant role of the viral late genes, in particular the DNA packaging genes, to enhance Ad oncolysis.
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA. slwech01@louisville.edu.|Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40202, USA. slwech01@louisville.edu.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Wechman
authors.affiliation: Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40202, USA. x0rao001@louisville.edu.|James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA. x0rao001@louisville.edu.
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Rao
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA. mcmasters@louisville.edu.|Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40202, USA. mcmasters@louisville.edu.|James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA. mcmasters@louisville.edu.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: McMasters
authors.affiliation: Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40202, USA. hszhou01@louisville.edu.|James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA. hszhou01@louisville.edu.|Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40202, USA. hszhou01@louisville.edu.
authors.forename: Heshan Sam
authors.initials: HS
authors.lastname: Zhou
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000502:physiology* / Q000528:radiation effects; D004252:DNA Mutational Analysis; D042003:DNA Packaging; D009154:Mutation; D050504:Oncolytic Viruses / Q000235:genetics* / Q000502:physiology* / Q000528:radiation effects; D014466:Ultraviolet Rays; D014764:Viral Proteins / Q000235:genetics; D057074:Virus Release
chemical_list: D014764:Viral Proteins
keywords: E1b; UV-irradiation; adenovirus; genomics; lung cancer