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Satellite Subgenomic Particles Are Key Regulators of Adeno-Associated Virus Life Cycle
Historically, adeno-associated virus (AAV)-defective interfering particles (DI) were known as abnormal virions arising from natural replication and encapsidation errors. Through single virion genome analysis, we revealed that a major category of DI particles contains a double-stranded DNA genome in...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235507/ https://www.ncbi.nlm.nih.gov/pubmed/34205760 http://dx.doi.org/10.3390/v13061185 |
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author | Zhang, Junping Yu, Xiangping Guo, Ping Firrman, Jenni Pouchnik, Derek Diao, Yong Samulski, Richard Jude Xiao, Weidong |
author_facet | Zhang, Junping Yu, Xiangping Guo, Ping Firrman, Jenni Pouchnik, Derek Diao, Yong Samulski, Richard Jude Xiao, Weidong |
author_sort | Zhang, Junping |
collection | PubMed |
description | Historically, adeno-associated virus (AAV)-defective interfering particles (DI) were known as abnormal virions arising from natural replication and encapsidation errors. Through single virion genome analysis, we revealed that a major category of DI particles contains a double-stranded DNA genome in a “snapback” configuration. The 5′- snapback genomes (SBGs) include the P5 promoters and partial rep gene sequences. The 3′-SBGs contains the capsid region. The molecular configuration of 5′-SBGs theoretically may allow double-stranded RNA transcription in their dimer configuration. Our studies demonstrated that 5-SBG regulated AAV rep expression and improved AAV packaging. In contrast, 3′-SBGs at its dimer configuration increased levels of cap protein. The generation and accumulation of 5′-SBGs and 3′-SBGs appears to be coordinated to balance the viral gene expression level. Therefore, the functions of 5′-SBGs and 3′-SBGs may help maximize the yield of AAV progenies. We postulate that AAV virus population behaved as a colony and utilizes its subgenomic particles to overcome the size limit of a viral genome and encodes additional essential functions. |
format | Online Article Text |
id | pubmed-8235507 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-82355072021-06-27 Satellite Subgenomic Particles Are Key Regulators of Adeno-Associated Virus Life Cycle Zhang, Junping Yu, Xiangping Guo, Ping Firrman, Jenni Pouchnik, Derek Diao, Yong Samulski, Richard Jude Xiao, Weidong Viruses Article Historically, adeno-associated virus (AAV)-defective interfering particles (DI) were known as abnormal virions arising from natural replication and encapsidation errors. Through single virion genome analysis, we revealed that a major category of DI particles contains a double-stranded DNA genome in a “snapback” configuration. The 5′- snapback genomes (SBGs) include the P5 promoters and partial rep gene sequences. The 3′-SBGs contains the capsid region. The molecular configuration of 5′-SBGs theoretically may allow double-stranded RNA transcription in their dimer configuration. Our studies demonstrated that 5-SBG regulated AAV rep expression and improved AAV packaging. In contrast, 3′-SBGs at its dimer configuration increased levels of cap protein. The generation and accumulation of 5′-SBGs and 3′-SBGs appears to be coordinated to balance the viral gene expression level. Therefore, the functions of 5′-SBGs and 3′-SBGs may help maximize the yield of AAV progenies. We postulate that AAV virus population behaved as a colony and utilizes its subgenomic particles to overcome the size limit of a viral genome and encodes additional essential functions. MDPI 2021-06-21 /pmc/articles/PMC8235507/ /pubmed/34205760 http://dx.doi.org/10.3390/v13061185 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zhang, Junping Yu, Xiangping Guo, Ping Firrman, Jenni Pouchnik, Derek Diao, Yong Samulski, Richard Jude Xiao, Weidong Satellite Subgenomic Particles Are Key Regulators of Adeno-Associated Virus Life Cycle |
title | Satellite Subgenomic Particles Are Key Regulators of Adeno-Associated Virus Life Cycle |
title_full | Satellite Subgenomic Particles Are Key Regulators of Adeno-Associated Virus Life Cycle |
title_fullStr | Satellite Subgenomic Particles Are Key Regulators of Adeno-Associated Virus Life Cycle |
title_full_unstemmed | Satellite Subgenomic Particles Are Key Regulators of Adeno-Associated Virus Life Cycle |
title_short | Satellite Subgenomic Particles Are Key Regulators of Adeno-Associated Virus Life Cycle |
title_sort | satellite subgenomic particles are key regulators of adeno-associated virus life cycle |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235507/ https://www.ncbi.nlm.nih.gov/pubmed/34205760 http://dx.doi.org/10.3390/v13061185 |
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