title: Adeno-associated virus enhances wild-type and oncolytic adenovirus spread.
abstract: The contamination of adenovirus (Ad) stocks with adeno-associated viruses (AAV) is usually unnoticed, and it has been associated with lower Ad yields upon large-scale production. During Ad propagation, AAV contamination needs to be detected routinely by polymerase chain reaction without symptomatic suspicion. In this study, we describe that the coinfection of either Ad wild type 5 or oncolytic Ad with AAV results in a large-plaque phenotype associated with an accelerated release of Ad from coinfected cells. This accelerated release was accompanied with the expected decrease in Ad yields in two out of three cell lines tested. Despite this lower Ad yield, coinfection with AAV accelerated cell death and enhanced the cytotoxicity mediated by Ad propagation. Intratumoral coinjection of Ad and AAV in two xenograft tumor models improved antitumor activity and mouse survival. Therefore, we conclude that accidental or intentional AAV coinfection has important implications for Ad-mediated virotherapy.
authors.affiliation: 1 Translational Research Laboratory, IDIBELL-Institut Català d'Oncologia , L'Hospitalet de Llobregat, 08907 Barcelona, Spain .
authors.forename: Eduardo
authors.initials: E
authors.lastname: Laborda
authors.forename: Cristina
authors.initials: C
authors.lastname: Puig-Saus
authors.forename: Manel
authors.initials: M
authors.lastname: Cascalló
authors.forename: Miguel
authors.initials: M
authors.lastname: Chillón
authors.forename: Ramon
authors.initials: R
authors.lastname: Alemany
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D059018:DNA Contamination; D000229:Dependovirus / Q000235:genetics*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000628:therapy; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics*; D014162:Transfection / Q000379:methods* / Q000592:standards; D023041:Xenograft Model Antitumor Assays
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