title: RNAi suppressor P19 can be broadly exploited for enhanced adenovirus replication and microRNA knockdown experiments.
abstract: RNA interference (RNAi) is a key regulator of various biological systems including viral infection. Within a virus life cycle gene products can be modulated by the RNA interference (RNAi) pathway which can crucially impact productive virus replication. Herein we explored the RNA interference suppressor protein P19 derived from a plant virus and we found that P19 enhanced adenovirus replication up to 100-fold. Critical factors responsible for this observation were overexpression of adenovirus encoded genes on mRNA and protein levels. To investigate the impact of this phenomenon on recombinant viruses, we exploited its feasibility for therapeutic and genomic applications. We found that P19 significantly increased recombinant adenovirus yields enabling up-scaling for preclinical and clinical studies. Moreover, adenoviruses possessed significantly higher oncolytic activity by expression of P19. Finally, we show that introducing a p19 expression cassette into high-capacity adenovirus provides a strategy to analyze RNAi knockdown in a tissue-specific manner.
authors: Max von Pettenkofer-Institute, Department of Virology, Ludwig-Maximilians-University Munich, 80336 Munich, Germany.
authors: Christina
authors: C
authors: Rauschhuber
authors: Martin
authors: M
authors: Mueck-Haeusl
authors: Wenli
authors: W
authors: Zhang
authors: Dirk M
authors: DM
authors: Nettelbeck
authors: Anja
authors: A
authors: Ehrhardt
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000502:physiology; D045744:Cell Line, Tumor; D003588:Cytopathogenic Effect, Viral; D015967:Gene Expression Regulation, Viral; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D050504:Oncolytic Viruses / Q000235:genetics; D009928:Organ Specificity / Q000235:genetics; D034622:RNA Interference; D014161:Transduction, Genetic; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
chemical_list: D035683:MicroRNAs; C493885:P19 protein, tomato bushy stunt virus; D014764:Viral Proteins