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Journal of Virology, August 2004, p. 8917-8921, Vol. 78, No. 16
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.16.8917-8921.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Characterization of the Mouse Adeno-Associated Virus AAVS1 Ortholog

Nathalie Dutheil,1 Miran Yoon-Robarts,1 Peter Ward,1 Els Henckaerts,1 Lucy Skrabanek,2,{dagger} Kenneth I. Berns,3 Fabien Campagne,2,{dagger} and R. Michael Linden1*

Carl C. Icahn Institute for Gene Therapy and Molecular Medicine,1 Department of Physiology and Biophysics, Institute for Computational Biomedicine, Mount Sinai School of Medicine, New York, New York 10029,2 Genetics Institute, University of Florida, Gainesville, Florida 326103

Received 21 January 2004/ Accepted 26 March 2004

The nonpathogenic human adeno-associated virus (AAV) has developed a mechanism to integrate its genome into human chromosome 19 at 19q13.4 (termed AAVS1), thereby establishing latency. Here, we provide evidence that the chromosomal signals required for site-specific integration are conserved in the mouse genome proximal to the recently identified Mbs85 gene. These sequence motifs can be specifically nicked by the viral Rep protein required for the initiation of site-specific AAV DNA integration. Furthermore, these signals can serve as a minimal origin for Rep-dependent DNA replication. In addition, we isolated the mouse Mbs85 proximal promoter and show transcriptional activity in three mouse cell lines.


* Corresponding author. Mailing address: Carl C. Icahn Institute for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Pl., Box 1496, New York, NY 10029. Phone: (212) 659-8278. Fax: (212) 849-2437. E-mail: Michael.Linden{at}mssm.edu.

{dagger} Present address: Weill Medical College of Cornell University, c/o Rockefeller University, New York, NY 10021.


Journal of Virology, August 2004, p. 8917-8921, Vol. 78, No. 16
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.16.8917-8921.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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