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Journal of Virology, April 2003, p. 4881-4887, Vol. 77, No. 8
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.8.4881-4887.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Packaging of Human Chromosome 19-Specific Adeno-Associated Virus (AAV) Integration Sites in AAV Virions during AAV Wild-Type and Recombinant AAV Vector Production

Daniela Hüser, Stefan Weger, and Regine Heilbronn*

Department of Virology, Institute of Infectious Diseases, Free University of Berlin, 12203 Berlin, Germany

Received 15 August 2002/ Accepted 17 January 2003

Adeno-associated virus type 2 (AAV-2) establishes latency by site-specific integration into a unique locus on human chromosome 19, called AAVS1. During the development of a sensitive real-time PCR assay for site-specific integration, AAV-AAVS1 junctions were reproducibly detected in highly purified AAV wild-type and recombinant AAV vector stocks. A series of controls documented that the junctions were packaged in AAV capsids and were newly generated during a single round of AAV production. Cloned junctions displayed variable AAV sequences fused to AAVS1. These data suggest that packaged junctions represent footprints of AAV integration during productive infection. Apparently, AAV latency established by site-specific integration and the helper virus-dependent, productive AAV cycle are more closely related than previously thought.

* Corresponding author. Mailing address: Institut für Infektionsmedizin, Abteilung Virologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 27, 12203 Berlin, Germany. Phone: 030-8445-3696. Fax: 030-8445-4485. E-mail: regine.heilbronn{at}ukbf.fu-berlin.de.

Journal of Virology, April 2003, p. 4881-4887, Vol. 77, No. 8
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.8.4881-4887.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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