High-throughput sequencing reveals principles of adeno-associated virus serotype 2 integration. Academic Article uri icon

Overview

abstract

  • Viral integrations are important in human biology, yet genome-wide integration profiles have not been determined for many viruses. Adeno-associated virus (AAV) infects most of the human population and is a prevalent gene therapy vector. AAV integrates into the human genome with preference for a single locus, termed AAVS1. However, the genome-wide integration of AAV has not been defined, and the principles underlying this recombination remain unclear. Using a novel high-throughput approach, integrant capture sequencing, nearly 12 million AAV junctions were recovered from a human cell line, providing five orders of magnitude more data than were previously available. Forty-five percent of integrations occurred near AAVS1, and several thousand novel integration hotspots were identified computationally. Most of these occurred in genes, with dozens of hotspots targeting known oncogenes. Viral replication protein binding sites (RBS) and transcriptional activity were major factors favoring integration. In a first for eukaryotic viruses, the data reveal a unique asymmetric integration profile with distinctive directional orientation of viral genomes. These studies provide a new understanding of AAV integration biology through the use of unbiased high-throughput data acquisition and bioinformatics.

publication date

  • May 29, 2013

Research

keywords

  • Dependovirus
  • Virus Integration

Identity

PubMed Central ID

  • PMC3719808

Scopus Document Identifier

  • 84880584473

Digital Object Identifier (DOI)

  • 10.1371/journal.pbio.1001046

PubMed ID

  • 23720718

Additional Document Info

volume

  • 87

issue

  • 15