Characterization of the Mouse Adeno-Associated Virus AAVS1 Ortholog

Author:

Dutheil Nathalie1,Yoon-Robarts Miran1,Ward Peter1,Henckaerts Els1,Skrabanek Lucy2,Berns Kenneth I.3,Campagne Fabien2,Linden R. Michael1

Affiliation:

1. Carl C. Icahn Institute for Gene Therapy and Molecular Medicine

2. Department of Physiology and Biophysics, Institute for Computational Biomedicine, Mount Sinai School of Medicine, New York, New York 10029

3. Genetics Institute, University of Florida, Gainesville, Florida 32610

Abstract

ABSTRACT 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.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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3. Bakowska, J. C., M. V. Di Maria, S. M. Camp, Y. Wang, P. D. Allen, and X. O. Breakefield. 2003. Targeted transgene integration into transgenic mouse fibroblasts carrying the full-length human AAVS1 locus mediated by HSV/AAV rep(+) hybrid amplicon vector. Gene Ther.10:1691-1702.

4. Adeno-associated virus Rep78 protein and terminal repeats enhance integration of DNA sequences into the cellular genome

5. Berns, K. I. 1996. Parvoviridae: the viruses and their replication, p. 2173-2197. In B. N. Fields, D. M. Knipe, and P. M. Howley (ed.), Fields virology, 3rd ed., vol. 2. Lippincott-Raven, Philadelphia, Pa.

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