RNAi suppressor P19 can be broadly exploited for enhanced adenovirus replication and microRNA knockdown experiments

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 suppres...

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Main Authors:	Rauschhuber, Christina, Mueck-Haeusl, Martin, Zhang, Wenli, Nettelbeck, Dirk M., Ehrhardt, Anja
Format:	Online
Language:	English
Published:	Nature Publishing Group 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586813/

id	pubmed-3586813
recordtype	oai_dc
spelling	pubmed-35868132013-03-06 RNAi suppressor P19 can be broadly exploited for enhanced adenovirus replication and microRNA knockdown experiments Rauschhuber, Christina Mueck-Haeusl, Martin Zhang, Wenli Nettelbeck, Dirk M. Ehrhardt, Anja Article 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. Nature Publishing Group 2013-03-04 /pmc/articles/PMC3586813/ /pubmed/23455436 http://dx.doi.org/10.1038/srep01363 Text en Copyright © 2013, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Rauschhuber, Christina Mueck-Haeusl, Martin Zhang, Wenli Nettelbeck, Dirk M. Ehrhardt, Anja
spellingShingle	Rauschhuber, Christina Mueck-Haeusl, Martin Zhang, Wenli Nettelbeck, Dirk M. Ehrhardt, Anja RNAi suppressor P19 can be broadly exploited for enhanced adenovirus replication and microRNA knockdown experiments
author_facet	Rauschhuber, Christina Mueck-Haeusl, Martin Zhang, Wenli Nettelbeck, Dirk M. Ehrhardt, Anja
author_sort	Rauschhuber, Christina
title	RNAi suppressor P19 can be broadly exploited for enhanced adenovirus replication and microRNA knockdown experiments
title_short	RNAi suppressor P19 can be broadly exploited for enhanced adenovirus replication and microRNA knockdown experiments
title_full	RNAi suppressor P19 can be broadly exploited for enhanced adenovirus replication and microRNA knockdown experiments
title_fullStr	RNAi suppressor P19 can be broadly exploited for enhanced adenovirus replication and microRNA knockdown experiments
title_full_unstemmed	RNAi suppressor P19 can be broadly exploited for enhanced adenovirus replication and microRNA knockdown experiments
title_sort	rnai suppressor p19 can be broadly exploited for enhanced adenovirus replication and microrna knockdown experiments
description	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.
publisher	Nature Publishing Group
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586813/
_version_	1611959040916586496

RNAi suppressor P19 can be broadly exploited for enhanced adenovirus replication and microRNA knockdown experiments

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