Highly divergent integration profile of adeno-associated virus serotype 5 revealed by high-throughput sequencing Journal Article
| Authors: | Janovitz, T.; Oliveira, T.; Sadelain, M.; Falck-Pedersen, E. |
| Article Title: | Highly divergent integration profile of adeno-associated virus serotype 5 revealed by high-throughput sequencing |
| Abstract: | Adeno-associated virus serotype 5 (AAV-5) is a human parvovirus that infects a high percentage of the population. It is the most divergent AAV, the DNA sequence cleaved by the viral endonuclease is distinct from all other described serotypes and, uniquely, AAV-5 does not cross-complement the replication of other serotypes. In contrast to the well-characterized integration of AAV-2, no published studies have investigated the genomic integration of AAV-5. In this study, we analyzed more than 660,000 AAV-5 integration junctions using high-throughput integrant capture sequencing of infected human cells. The integration activity of AAV-5 was 99.7% distinct from AAV-2 and favored intronic sequences. Genome-wide integration was highly correlated with viral replication protein binding and endonuclease sites, and a 39-bp consensus integration motif was revealed that included these features. Algorithmic scanning identified 126 AAV-5 hot spots, the largest of which encompassed 3.3% of all integration events. The unique aspects of AAV-5 integration may provide novel tools for biotechnology and gene therapy. © 2014, American Society for Microbiology. |
| Keywords: | human cell; dna-binding proteins; nonhuman; gene; protein dna binding; cell line; genetic association; base sequence; binding sites; virus replication; endonuclease; chromosome mapping; viral proteins; enzyme active site; consensus sequence; genome, viral; endonucleases; virus dna cell dna interaction; virus integration; high throughput sequencing; gene order; high-throughput nucleotide sequencing; serotype; nucleotide motifs; adeno associated virus; dependovirus; humans; human; priority journal; article; adeno associated virus serotype 2; adeno associated virus serotype 5; bicc1 gene; mtmr12 gene; rbm19 gene; rimbp2 gene; slc7a9 gene; position-specific scoring matrices |
| Journal Title: | Journal of Virology |
| Volume: | 88 |
| Issue: | 5 |
| ISSN: | 0022-538X |
| Publisher: | American Society for Microbiology |
| Date Published: | 2014-03-01 |
| Start Page: | 2481 |
| End Page: | 2488 |
| Language: | English |
| DOI: | 10.1128/jvi.03419-13 |
| PROVIDER: | scopus |
| PUBMED: | 24335317 |
| PMCID: | PMC3958079 |
| DOI/URL: | |
| Notes: | Export Date: 3 March 2014 -- CODEN: JOVIA -- Source: Scopus |
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