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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doaj-275cbcab55314967ba25a3194c35263d2020-11-25T01:21:17ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012015-01-012Vaccinia virus as a subhelper for AAV replication and packagingAndrea R Moore0Biao Dong1Lingxia Chen2Weidong Xiao3Department of Microbiology and Immunology, Sol Sherry Thrombosis Research Center, Temple University, Philadelphia, Pennsylvania, USADepartment of Microbiology and Immunology, Sol Sherry Thrombosis Research Center, Temple University, Philadelphia, Pennsylvania, USADepartment of Microbiology and Immunology, Sol Sherry Thrombosis Research Center, Temple University, Philadelphia, Pennsylvania, USADepartment of Microbiology and Immunology, Sol Sherry Thrombosis Research Center, Temple University, Philadelphia, Pennsylvania, USAAdeno-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.http://www.sciencedirect.com/science/article/pii/S2329050116300560 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Andrea R Moore Biao Dong Lingxia Chen Weidong Xiao |
spellingShingle |
Andrea R Moore Biao Dong Lingxia Chen Weidong Xiao Vaccinia virus as a subhelper for AAV replication and packaging Molecular Therapy: Methods & Clinical Development |
author_facet |
Andrea R Moore Biao Dong Lingxia Chen Weidong Xiao |
author_sort |
Andrea R Moore |
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 |
publisher |
Elsevier |
series |
Molecular Therapy: Methods & Clinical Development |
issn |
2329-0501 |
publishDate |
2015-01-01 |
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. |
url |
http://www.sciencedirect.com/science/article/pii/S2329050116300560 |
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