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...
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| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/6/1185 |
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| author | Junping Zhang Xiangping Yu Ping Guo Jenni Firrman Derek Pouchnik Yong Diao Richard Jude Samulski Weidong Xiao |
| author_facet | Junping Zhang Xiangping Yu Ping Guo Jenni Firrman Derek Pouchnik Yong Diao Richard Jude Samulski Weidong Xiao |
| author_sort | Junping Zhang |
| collection | DOAJ |
| 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 <i>rep</i> 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. |
| first_indexed | 2024-03-10T10:12:40Z |
| format | Article |
| id | doaj.art-6c6862290ff147d098db36135bb0a91e |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T10:12:40Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-6c6862290ff147d098db36135bb0a91e2023-11-22T01:04:19ZengMDPI AGViruses1999-49152021-06-01136118510.3390/v13061185Satellite Subgenomic Particles Are Key Regulators of Adeno-Associated Virus Life CycleJunping Zhang0Xiangping Yu1Ping Guo2Jenni Firrman3Derek Pouchnik4Yong Diao5Richard Jude Samulski6Weidong Xiao7School of Medicine, Huaqiao University, Quanzhou 362021, ChinaSchool of Medicine, Huaqiao University, Quanzhou 362021, ChinaSchool of Medicine, Huaqiao University, Quanzhou 362021, ChinaDairy and Functional Foods Research Unit, Eastern Regional Research Center, Agricultural Research Service, U.S. Department of Agriculture, Wyndmoor, PA 19038, USASchool of Molecular Biosciences, Washington State University, Pullman, WA 99164, USASchool of Medicine, Huaqiao University, Quanzhou 362021, ChinaDepartment of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAHerman B Wells Center for Pediatric Research, Indiana University, Indianapolis, IN 46202, USAHistorically, 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 <i>rep</i> 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.https://www.mdpi.com/1999-4915/13/6/1185adeno-associated virussubgenomic particles“snapback” configurationlife cycle |
| spellingShingle | Junping Zhang Xiangping Yu Ping Guo Jenni Firrman Derek Pouchnik Yong Diao Richard Jude Samulski Weidong Xiao Satellite Subgenomic Particles Are Key Regulators of Adeno-Associated Virus Life Cycle Viruses adeno-associated virus subgenomic particles “snapback” configuration 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 | adeno-associated virus subgenomic particles “snapback” configuration life cycle |
| url | https://www.mdpi.com/1999-4915/13/6/1185 |
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