Journal article
Formation of Adeno-Associated Virus Circular Genomes Is Differentially Regulated by Adenovirus E4 ORF6 and E2a Gene Expression
Journal of virology, Vol.73(1), pp.161-169
01/1999
DOI: 10.1128/JVI.73.1.161-169.1999
PMCID: PMC103819
PMID: 9847318
Abstract
ABSTRACT
A central feature of the adeno-associated virus (AAV) latent life cycle is persistence in the form of both integrated and episomal genomes. However, the molecular processes associated with episomal long-term persistence of AAV genomes are only poorly understood. To investigate these mechanisms, we have utilized a recombinant AAV (rAAV) shuttle vector to identify circular AAV intermediates from transduced HeLa cells and primary fibroblasts. The unique structural features exhibited by these transduction intermediates included circularized monomer and dimer virus genomes in a head-to-tail array, with associated specific base pair alterations in the 5′ viral D sequence. In HeLa cells, the abundance and stability of AAV circular intermediates were augmented by adenovirus expressing the E2a gene product. In the absence of E2a, adenovirus expressing the E4 open reading frame 6 gene product decreased the abundance of AAV circular intermediates, favoring instead the linear replication form monomer (Rf
m
) and dimer (Rf
d
) structures. In summary, the formation of AAV circular intermediates appears to represent a new pathway for AAV genome conversion, which is consistent with the head-to-tail concatemerization associated with latent-phase persistence of rAAV. A better understanding of this pathway may increase the utility of rAAV vectors for gene therapy.
Details
- Title: Subtitle
- Formation of Adeno-Associated Virus Circular Genomes Is Differentially Regulated by Adenovirus E4 ORF6 and E2a Gene Expression
- Creators
- Dongsheng Duan - University of IowaPrerna Sharma - University of IowaLorita Dudus - University Medical Center New OrleansYulong Zhang - University of IowaSalih Sanlioglu - University of IowaZiying Yan - University of IowaYongping Yue - University of IowaYihong Ye - University of IowaRachael Lester - University of IowaJusan Yang - University of IowaKrishna J. Fisher - University Medical Center New OrleansJohn F. Engelhardt - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.73(1), pp.161-169
- DOI
- 10.1128/JVI.73.1.161-169.1999
- PMID
- 9847318
- PMCID
- PMC103819
- NLM abbreviation
- J Virol
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Language
- English
- Date published
- 01/1999
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984284340502771
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