Vaccinia virus as a subhelper for AAV replication and packaging

Adeno-associated virus (AAV) has been widely used as a gene therapy vector to treat a variety of disorders. While these vectors are increasingly popular and successful in the clinic, there is still much to learn about the viruses. Understanding the biology of these viruses is essential in engineerin...

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Main Authors:	Moore, Andrea R, Dong, Biao, Chen, Lingxia, Xiao, Weidong
Format:	Online
Language:	English
Published:	Nature Publishing Group 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4650997/

id	pubmed-4650997
recordtype	oai_dc
spelling	pubmed-46509972015-12-03 Vaccinia virus as a subhelper for AAV replication and packaging Moore, Andrea R Dong, Biao Chen, Lingxia Xiao, Weidong Article Adeno-associated virus (AAV) has been widely used as a gene therapy vector to treat a variety of disorders. While these vectors are increasingly popular and successful in the clinic, there is still much to learn about the viruses. Understanding the biology of these viruses is essential in engineering better vectors and generating vectors more efficiently for large-scale use. AAV requires a helper for production and replication making this aspect of the viral life cycle crucial. Vaccinia virus (VV) has been widely cited as a helper virus for AAV. However, to date, there are no detailed analyses of its helper function. Here, the helper role of VV was studied in detail. In contrast to common belief, we demonstrated that VV was not a sufficient helper virus for AAV replication. Vaccinia failed to produce rAAV and activate AAV promoters. While this virus could not support rAAV production, Vaccinia could initiate AAV replication and packaging when AAV promoter activation is not necessary. This activity is due to the ability of Vaccinia-driven Rep78 to transcribe in the cytoplasm and subsequently translate in the nucleus and undergo typical functions in the AAV life cycle. As such, VV is subhelper for AAV compared to complete helper functions of adenovirus. Nature Publishing Group 2015-11-18 /pmc/articles/PMC4650997/ /pubmed/26636113 http://dx.doi.org/10.1038/mtm.2015.44 Text en Copyright © 2015 Official journal of the American Society of Gene & Cell Therapy http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
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	Moore, Andrea R Dong, Biao Chen, Lingxia Xiao, Weidong
spellingShingle	Moore, Andrea R Dong, Biao Chen, Lingxia Xiao, Weidong Vaccinia virus as a subhelper for AAV replication and packaging
author_facet	Moore, Andrea R Dong, Biao Chen, Lingxia Xiao, Weidong
author_sort	Moore, Andrea R
title	Vaccinia virus as a subhelper for AAV replication and packaging
title_short	Vaccinia virus as a subhelper for AAV replication and packaging
title_full	Vaccinia virus as a subhelper for AAV replication and packaging
title_fullStr	Vaccinia virus as a subhelper for AAV replication and packaging
title_full_unstemmed	Vaccinia virus as a subhelper for AAV replication and packaging
title_sort	vaccinia virus as a subhelper for aav replication and packaging
description	Adeno-associated virus (AAV) has been widely used as a gene therapy vector to treat a variety of disorders. While these vectors are increasingly popular and successful in the clinic, there is still much to learn about the viruses. Understanding the biology of these viruses is essential in engineering better vectors and generating vectors more efficiently for large-scale use. AAV requires a helper for production and replication making this aspect of the viral life cycle crucial. Vaccinia virus (VV) has been widely cited as a helper virus for AAV. However, to date, there are no detailed analyses of its helper function. Here, the helper role of VV was studied in detail. In contrast to common belief, we demonstrated that VV was not a sufficient helper virus for AAV replication. Vaccinia failed to produce rAAV and activate AAV promoters. While this virus could not support rAAV production, Vaccinia could initiate AAV replication and packaging when AAV promoter activation is not necessary. This activity is due to the ability of Vaccinia-driven Rep78 to transcribe in the cytoplasm and subsequently translate in the nucleus and undergo typical functions in the AAV life cycle. As such, VV is subhelper for AAV compared to complete helper functions of adenovirus.
publisher	Nature Publishing Group
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4650997/
_version_	1613503331697688576

Vaccinia virus as a subhelper for AAV replication and packaging

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