title: Adenoviruses induce autophagy to promote virus replication and oncolysis.
abstract: Adenoviruses with deletion of E1b have been used in clinical trials to treat cancers that are resistant to conventional therapies. The efficacy of viral replication within cancer cells determines the results of oncolytic therapy, which remains poorly understood and requires further improvement. In this report, we show that adenoviruses induce autophagy by increasing the conversion of LC3-I to LC3-II and the formation of the Atg12-Atg5 complex. Inhibition of autophagy with 3-methyladenine (3MA) resulted in a decreased synthesis of adenovirus structural proteins, and thereby a poor viral replication; promotion of autophagy with rapamycin increased adenovirus yield. This study indicates that adenovirus-induced autophagy correlates positively with virus replication and oncolytic cell death, and that autophagy may generate nutrients that can be used for building viral progeny particles. These results further suggest that chemotherapeutic agents that increase cancer cell autophagy may improve the efficacy of oncolytic virotherapy.
authors.affiliation: Department of Surgery, University of Louisville School of Medicine, KY 40292, USA.
authors.forename: Humberto
authors.initials: H
authors.lastname: Rodriguez-Rocha
authors.forename: Jorge G
authors.initials: JG
authors.lastname: Gomez-Gutierrez
authors.forename: Aracely
authors.initials: A
authors.lastname: Garcia-Garcia
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Rao
authors.forename: Lan
authors.initials: L
authors.lastname: Chen
authors.forename: Kelly M
authors.initials: KM
authors.lastname: McMasters
authors.forename: Heshan Sam
authors.initials: HS
authors.lastname: Zhou
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000256:Adenoviridae / Q000502:physiology*; D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism; D017501:Adenovirus E1B Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D000071192:Autophagy-Related Protein 12; D000071187:Autophagy-Related Protein 5; D045744:Cell Line, Tumor; D015967:Gene Expression Regulation, Viral; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009154:Mutation; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology*
chemical_list: C466624:ATG12 protein, human; C502778:ATG5 protein, human; D017500:Adenovirus E1A Proteins; D017501:Adenovirus E1B Proteins; D000071192:Autophagy-Related Protein 12; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; C025946:3-methyladenine; D000225:Adenine