title: Oncolytic Replication of E1b-Deleted Adenoviruses.
abstract: Various viruses have been studied and developed for oncolytic virotherapies. In virotherapy, a relatively small amount of viruses used in an intratumoral injection preferentially replicate in and lyse cancer cells, leading to the release of amplified viral particles that spread the infection to the surrounding tumor cells and reduce the tumor mass. Adenoviruses (Ads) are most commonly used for oncolytic virotherapy due to their infection efficacy, high titer production, safety, easy genetic modification, and well-studied replication characteristics. Ads with deletion of E1b55K preferentially replicate in and destroy cancer cells and have been used in multiple clinical trials. H101, one of the E1b55K-deleted Ads, has been used for the treatment of late-stage cancers as the first approved virotherapy agent. However, the mechanism of selective replication of E1b-deleted Ads in cancer cells is still not well characterized. This review will focus on three potential molecular mechanisms of oncolytic replication of E1b55K-deleted Ads. These mechanisms are based upon the functions of the viral E1B55K protein that are associated with p53 inhibition, late viralmRNAexport, and cell cycle disruption.
authors.affiliation: Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. paisin.paisin@gmail.com.
authors.forename: Pei-Hsin
authors.initials: PH
authors.lastname: Cheng
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40292, USA. slwech01@exchange.louisville.edu.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Wechman
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40292, USA. mcmasters@louisville.edu.|Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40292, 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 40292, USA. hszhou01@louisville.edu.|James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40292, USA. hszhou01@louisville.edu.|Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40292, USA. hszhou01@louisville.edu.
authors.forename: Heshan Sam
authors.initials: HS
authors.lastname: Zhou
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D017501:Adenovirus E1B Proteins / Q000172:deficiency* / Q000235:genetics; D017353:Gene Deletion; D006801:Humans; D050504:Oncolytic Viruses / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication
chemical_list: D017501:Adenovirus E1B Proteins
keywords: E1B; adenovirus; cancer selectivity; cell cycle; cyclin E; virotherapy