Development of non-defective recombinant densovirus vectors for microRNA delivery in the invasive vector mosquito, Aedes albopictus

We previously reported that mosquito densoviruses (MDVs) are potential vectors for delivering foreign nucleic acids into mosquito cells. However, considering existing expression strategies, recombinant viruses would inevitably become replication-defective viruses and lose their ability for secondary...

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Main Authors: Liu, Peiwen, Li, Xiaocong, Gu, Jinbao, Dong, Yunqiao, Liu, Yan, Santhosh, Puthiyakunnon, Chen, Xiaoguang
Format: Online
Language:English
Published: Nature Publishing Group 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754678/
id pubmed-4754678
recordtype oai_dc
spelling pubmed-47546782016-02-24 Development of non-defective recombinant densovirus vectors for microRNA delivery in the invasive vector mosquito, Aedes albopictus Liu, Peiwen Li, Xiaocong Gu, Jinbao Dong, Yunqiao Liu, Yan Santhosh, Puthiyakunnon Chen, Xiaoguang Article We previously reported that mosquito densoviruses (MDVs) are potential vectors for delivering foreign nucleic acids into mosquito cells. However, considering existing expression strategies, recombinant viruses would inevitably become replication-defective viruses and lose their ability for secondary transmission. The packaging limitations of the virion represent a barrier for the development of MDVs for viral paratransgenesis or as high-efficiency bioinsecticides. Herein, we report the development of a non-defective recombinant Aedes aegypti densovirus (AaeDV) miRNA expression system, mediated by an artificial intron, using an intronic miRNA expression strategy. We demonstrated that this recombinant vector could be used to overexpress endogenous miRNAs or to decrease endogenous miRNAs by generating antisense sponges to explore the biological functions of miRNAs. In addition, the vector could express antisense-miRNAs to induce efficient gene silencing in vivo and in vitro. The recombinant virus effectively self-replicated and retained its secondary transmission ability, similar to the wild-type virus. The recombinant virus was also genetically stable. This study demonstrated the first construction of a non-defective recombinant MDV miRNA expression system, which represents a tool for the functional analysis of mosquito genes and lays the foundation for the application of viral paratransgenesis for dengue virus control. Nature Publishing Group 2016-02-16 /pmc/articles/PMC4754678/ /pubmed/26879823 http://dx.doi.org/10.1038/srep20979 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 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/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 Liu, Peiwen
Li, Xiaocong
Gu, Jinbao
Dong, Yunqiao
Liu, Yan
Santhosh, Puthiyakunnon
Chen, Xiaoguang
spellingShingle Liu, Peiwen
Li, Xiaocong
Gu, Jinbao
Dong, Yunqiao
Liu, Yan
Santhosh, Puthiyakunnon
Chen, Xiaoguang
Development of non-defective recombinant densovirus vectors for microRNA delivery in the invasive vector mosquito, Aedes albopictus
author_facet Liu, Peiwen
Li, Xiaocong
Gu, Jinbao
Dong, Yunqiao
Liu, Yan
Santhosh, Puthiyakunnon
Chen, Xiaoguang
author_sort Liu, Peiwen
title Development of non-defective recombinant densovirus vectors for microRNA delivery in the invasive vector mosquito, Aedes albopictus
title_short Development of non-defective recombinant densovirus vectors for microRNA delivery in the invasive vector mosquito, Aedes albopictus
title_full Development of non-defective recombinant densovirus vectors for microRNA delivery in the invasive vector mosquito, Aedes albopictus
title_fullStr Development of non-defective recombinant densovirus vectors for microRNA delivery in the invasive vector mosquito, Aedes albopictus
title_full_unstemmed Development of non-defective recombinant densovirus vectors for microRNA delivery in the invasive vector mosquito, Aedes albopictus
title_sort development of non-defective recombinant densovirus vectors for microrna delivery in the invasive vector mosquito, aedes albopictus
description We previously reported that mosquito densoviruses (MDVs) are potential vectors for delivering foreign nucleic acids into mosquito cells. However, considering existing expression strategies, recombinant viruses would inevitably become replication-defective viruses and lose their ability for secondary transmission. The packaging limitations of the virion represent a barrier for the development of MDVs for viral paratransgenesis or as high-efficiency bioinsecticides. Herein, we report the development of a non-defective recombinant Aedes aegypti densovirus (AaeDV) miRNA expression system, mediated by an artificial intron, using an intronic miRNA expression strategy. We demonstrated that this recombinant vector could be used to overexpress endogenous miRNAs or to decrease endogenous miRNAs by generating antisense sponges to explore the biological functions of miRNAs. In addition, the vector could express antisense-miRNAs to induce efficient gene silencing in vivo and in vitro. The recombinant virus effectively self-replicated and retained its secondary transmission ability, similar to the wild-type virus. The recombinant virus was also genetically stable. This study demonstrated the first construction of a non-defective recombinant MDV miRNA expression system, which represents a tool for the functional analysis of mosquito genes and lays the foundation for the application of viral paratransgenesis for dengue virus control.
publisher Nature Publishing Group
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754678/
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