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Journal of Virology, November 2004, p. 11656-11663, Vol. 78, No. 21
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.21.11656-11663.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Genome-Wide Analyses of Avian Sarcoma Virus Integration Sites

Anna Narezkina, Konstantin D. Taganov,{dagger} Samuel Litwin, Radka Stoyanova, Junpei Hayashi, Christoph Seeger, Anna Marie Skalka, and Richard A. Katz*

Fox Chase Cancer Center, Institute for Cancer Research, Philadelphia, Pennsylvania

Received 31 March 2004/ Accepted 28 June 2004

The chromosomal features that influence retroviral integration site selection are not well understood. Here, we report the mapping of 226 avian sarcoma virus (ASV) integration sites in the human genome. The results show that the sites are distributed over all chromosomes, and no global bias for integration site selection was detected. However, RNA polymerase II transcription units (protein-encoding genes) appear to be favored targets of ASV integration. The integration frequency within genes is similar to that previously described for murine leukemia virus but distinct from the higher frequency observed with human immunodeficiency virus type 1. We found no evidence for preferred ASV integration sites over the length of genes and immediate flanking regions. Microarray analysis of uninfected HeLa cells revealed that the expression levels of ASV target genes were similar to the median level for all genes represented in the array. Although expressed genes were targets for integration, we found no preference for integration into highly expressed genes. Our results provide a more detailed description of the chromosomal features that may influence ASV integration and support the idea that distinct, virus-specific mechanisms mediate integration site selection. Such differences may be relevant to viral pathogenesis and provide utility in retroviral vector design.

* Corresponding author. Mailing address: Fox Chase Cancer Center, Institute for Cancer Research, 333 Cottman Ave., Philadelphia, PA 19111-2497. Phone: (215) 728-3668. Fax: (215) 728-2778. E-mail: r_katz{at}fccc.edu.

{dagger} Present address. California Institute of Technology, Pasadena, CA 91125.

Journal of Virology, November 2004, p. 11656-11663, Vol. 78, No. 21
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.21.11656-11663.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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