This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Narezkina, A. Articles by Katz, R. A. Search for Related Content PubMed PubMed Citation Articles by Narezkina, A. Articles by Katz, R. A.

Genome-Wide Analyses of Avian Sarcoma Virus Integration Sites

Anna Narezkina, Konstantin D. Taganov, 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.

Present address. California Institute of Technology, Pasadena, CA 91125.

This article has been cited by other articles:

• Poleshko, A., Palagin, I., Zhang, R., Boimel, P., Castagna, C., Adams, P. D., Skalka, A. M., Katz, R. A. (2008). Identification of Cellular Proteins That Maintain Retroviral Epigenetic Silencing: Evidence for an Antiviral Response. J. Virol. 82: 2313-2323 [Abstract] [Full Text]  
• Faschinger, A., Rouault, F., Sollner, J., Lukas, A., Salmons, B., Gunzburg, W. H., Indik, S. (2008). Mouse Mammary Tumor Virus Integration Site Selection in Human and Mouse Genomes. J. Virol. 82: 1360-1367 [Abstract] [Full Text]  
• Shun, M.-C., Raghavendra, N. K., Vandegraaff, N., Daigle, J. E., Hughes, S., Kellam, P., Cherepanov, P., Engelman, A. (2007). LEDGF/p75 functions downstream from preintegration complex formation to effect gene-specific HIV-1 integration. Genes Dev. 21: 1767-1778 [Abstract] [Full Text]  
• Derse, D., Crise, B., Li, Y., Princler, G., Lum, N., Stewart, C., McGrath, C. F., Hughes, S. H., Munroe, D. J., Wu, X. (2007). Human T-Cell Leukemia Virus Type 1 Integration Target Sites in the Human Genome: Comparison with Those of Other Retroviruses. J. Virol. 81: 6731-6741 [Abstract] [Full Text]  
• Drew, H. R., Lockett, L. J., Both, G. W. (2007). Increased complexity of wild-type adeno-associated virus-chromosomal junctions as determined by analysis of unselected cellular genomes. J. Gen. Virol. 88: 1722-1732 [Abstract] [Full Text]  
• Pandey, K. K., Sinha, S., Grandgenett, D. P. (2007). Transcriptional Coactivator LEDGF/p75 Modulates Human Immunodeficiency Virus Type 1 Integrase-Mediated Concerted Integration. J. Virol. 81: 3969-3979 [Abstract] [Full Text]  
• Katz, R. A., Jack-Scott, E., Narezkina, A., Palagin, I., Boimel, P., Kulkosky, J., Nicolas, E., Greger, J. G., Skalka, A. M. (2007). High-Frequency Epigenetic Repression and Silencing of Retroviruses Can Be Antagonized by Histone Deacetylase Inhibitors and Transcriptional Activators, but Uniform Reactivation in Cell Clones Is Restricted by Additional Mechanisms. J. Virol. 81: 2592-2604 [Abstract] [Full Text]  
• Cherepanov, P. (2007). LEDGF/p75 interacts with divergent lentiviral integrases and modulates their enzymatic activity in vitro. Nucleic Acids Res 35: 113-124 [Abstract] [Full Text]  
• Moalic, Y., Blanchard, Y., Felix, H., Jestin, A. (2006). Porcine Endogenous Retrovirus Integration Sites in the Human Genome: Features in Common with Those of Murine Leukemia Virus. J. Virol. 80: 10980-10988 [Abstract] [Full Text]  
• Kim, S., Kim, Y., Liang, T., Sinsheimer, J. S., Chow, S. A. (2006). A High-Throughput Method for Cloning and Sequencing Human Immunodeficiency Virus Type 1 Integration Sites. J. Virol. 80: 11313-11321 [Abstract] [Full Text]  
• MacNeil, A., Sankale, J.-L., Meloni, S. T., Sarr, A. D., Mboup, S., Kanki, P. (2006). Genomic Sites of Human Immunodeficiency Virus Type 2 (HIV-2) Integration: Similarities to HIV-1 In Vitro and Possible Differences In Vivo.. J. Virol. 80: 7316-7321 [Abstract] [Full Text]  
• Liu, H., Dow, E. C., Arora, R., Kimata, J. T., Bull, L. M., Arduino, R. C., Rice, A. P. (2006). Integration of Human Immunodeficiency Virus Type 1 in Untreated Infection Occurs Preferentially within Genes.. J. Virol. 80: 7765-7768 [Abstract] [Full Text]  
• Monse, H., Laufs, S., Kuate, S., Zeller, W. J., Fruehauf, S., Uberla, K. (2006). Viral determinants of integration site preferences of simian immunodeficiency virus-based vectors.. J. Virol. 80: 8145-8150 [Abstract] [Full Text]  
• Nowrouzi, A., Dittrich, M., Klanke, C., Heinkelein, M., Rammling, M., Dandekar, T., von Kalle, C., Rethwilm, A. (2006). Genome-wide mapping of foamy virus vector integrations into a human cell line.. J. Gen. Virol. 87: 1339-1347 [Abstract] [Full Text]  
• Trobridge, G. D., Miller, D. G., Jacobs, M. A., Allen, J. M., Kiem, H.-P., Kaul, R., Russell, D. W. (2006). Foamy virus vector integration sites in normal human cells. Proc. Natl. Acad. Sci. USA 103: 1498-1503 [Abstract] [Full Text]  
• Geurts, A. M., Hackett, C. S., Bell, J. B., Bergemann, T. L., Collier, L. S., Carlson, C. M., Largaespada, D. A., Hackett, P. B. (2006). Structure-based prediction of insertion-site preferences of transposons into chromosomes.. Nucleic Acids Res 34: 2803-2811 [Abstract] [Full Text]  
• Bradley, C. M., Craigie, R. (2005). Seeing is believing: Structure of the catalytic domain of HIV-1 integrase in complex with human LEDGF/p75. Proc. Natl. Acad. Sci. USA 102: 17543-17544 [Full Text]  
• Crise, B., Li, Y., Yuan, C., Morcock, D. R., Whitby, D., Munroe, D. J., Arthur, L. O., Wu, X. (2005). Simian Immunodeficiency Virus Integration Preference Is Similar to That of Human Immunodeficiency Virus Type 1. J. Virol. 79: 12199-12204 [Abstract] [Full Text]  
• Barr, S. D., Leipzig, J., Shinn, P., Ecker, J. R., Bushman, F. D. (2005). Integration Targeting by Avian Sarcoma-Leukosis Virus and Human Immunodeficiency Virus in the Chicken Genome. J. Virol. 79: 12035-12044 [Abstract] [Full Text]  
• Miller, D. G., Trobridge, G. D., Petek, L. M., Jacobs, M. A., Kaul, R., Russell, D. W. (2005). Large-Scale Analysis of Adeno-Associated Virus Vector Integration Sites in Normal Human Cells. J. Virol. 79: 11434-11442 [Abstract] [Full Text]  
• Grandgenett, D. P. (2005). Symmetrical recognition of cellular DNA target sequences during retroviral integration. Proc. Natl. Acad. Sci. USA 102: 5903-5904 [Full Text]  
• Holman, A. G., Coffin, J. M. (2005). Symmetrical base preferences surrounding HIV-1, avian sarcoma/leukosis virus, and murine leukemia virus integration sites. Proc. Natl. Acad. Sci. USA 102: 6103-6107 [Abstract] [Full Text]  
• Wu, X., Li, Y., Crise, B., Burgess, S. M., Munroe, D. J. (2005). Weak Palindromic Consensus Sequences Are a Common Feature Found at the Integration Target Sites of Many Retroviruses. J. Virol. 79: 5211-5214 [Abstract] [Full Text]  
• Yant, S. R., Wu, X., Huang, Y., Garrison, B., Burgess, S. M., Kay, M. A. (2005). High-Resolution Genome-Wide Mapping of Transposon Integration in Mammals. Mol. Cell. Biol. 25: 2085-2094 [Abstract] [Full Text]  
• Engelman, A. (2005). The ups and downs of gene expression and retroviral DNA integration. Proc. Natl. Acad. Sci. USA 102: 1275-1276 [Full Text]  
• Maxfield, L. F., Fraize, C. D., Coffin, J. M. (2005). From The Cover: Relationship between retroviral DNA-integration-site selection and host cell transcription. Proc. Natl. Acad. Sci. USA 102: 1436-1441 [Abstract] [Full Text]