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

 Previous Article  |  Next Article 

Journal of Virology, September 2000, p. 8382-8389, Vol. 74, No. 18
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Relationship between Retroviral DNA Integration and Gene Expression

Joanne Barnes Weidhaas, Elizabeth Lloyd Angelichio, Sabine Fenner, and John M. Coffin*

Department of Molecular Biology and Microbiology, Tufts University, Boston, Massachusetts 02111

Received 2 March 2000/Accepted 16 June 2000

Although retroviruses can integrate their DNA into a large number of sites in the host genome, factors controlling the specificity of integration remain controversial and poorly understood. To assess the effects of transcriptional activity on integration in vivo, we created quail cell clones containing a construct with a minigene cassette, whose expression is controlled by the papilloma virus E2 protein. From these clones we derived transcriptionally active subclones expressing the wild-type E2 protein and transcriptionally silent subclones expressing a mutant E2 protein that binds its target DNA but is unable to activate transcription. By infecting both clones and subclones with avian leukosis virus and using a PCR-based assay to determine viral DNA integration patterns, we were able to assess the effects of both protein binding and transcriptional activity on retroviral DNA integration. Contrary to the hypothesis that transcriptional activity enhances integration, we found an overall decrease in integration into our gene cassette in subclones expressing the wild-type E2 protein. We also found a decrease in integration into our gene cassette in subclones expressing the mutant E2 protein, but only into the protein binding region. Based on these findings, we propose that transcriptionally active DNA is not a preferred target for retroviral integration and that transcriptional activity may in fact be correlated with a decrease in integration.

* Corresponding author. Mailing address: Department of Molecular Biology and Microbiology, Tufts University, 136 Harrison Ave., Boston, MA 02111. Phone: (617) 636-6528. Fax: (617) 636-8086. E-mail: jcoffin_par{at}opal.tufts.edu.

Journal of Virology, September 2000, p. 8382-8389, Vol. 74, No. 18
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Vatakis, D. N., Kim, S., Kim, N., Chow, S. A., Zack, J. A. (2009). Human Immunodeficiency Virus Integration Efficiency and Site Selection in Quiescent CD4+ T Cells. J. Virol. 83: 6222-6233 [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]  
  • 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]  
  • 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]  
  • Narezkina, A., Taganov, K. D., Litwin, S., Stoyanova, R., Hayashi, J., Seeger, C., Skalka, A. M., Katz, R. A. (2004). Genome-Wide Analyses of Avian Sarcoma Virus Integration Sites. J. Virol. 78: 11656-11663 [Abstract] [Full Text]  
  • Han, Y., Lassen, K., Monie, D., Sedaghat, A. R., Shimoji, S., Liu, X., Pierson, T. C., Margolick, J. B., Siliciano, R. F., Siliciano, J. D. (2004). Resting CD4+ T Cells from Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Individuals Carry Integrated HIV-1 Genomes within Actively Transcribed Host Genes. J. Virol. 78: 6122-6133 [Abstract] [Full Text]  
  • Taganov, K. D., Cuesta, I., Daniel, R., Cirillo, L. A., Katz, R. A., Zaret, K. S., Skalka, A. M. (2004). Integrase-Specific Enhancement and Suppression of Retroviral DNA Integration by Compacted Chromatin Structure In Vitro. J. Virol. 78: 5848-5855 [Abstract] [Full Text]  
  • Violot, S., Hong, S. S., Rakotobe, D., Petit, C., Gay, B., Moreau, K., Billaud, G., Priet, S., Sire, J., Schwartz, O., Mouscadet, J.-F., Boulanger, P. (2003). The Human Polycomb Group EED Protein Interacts with the Integrase of Human Immunodeficiency Virus Type 1. J. Virol. 77: 12507-12522 [Abstract] [Full Text]  
  • Bowen, N. J., Jordan, I. K., Epstein, J. A., Wood, V., Levin, H. L. (2003). Retrotransposons and Their Recognition of pol II Promoters: A Comprehensive Survey of the Transposable Elements From the Complete Genome Sequence of Schizosaccharomyces pombe. Genome Res 13: 1984-1997 [Abstract] [Full Text]  
  • Khambata-Ford, S., Liu, Y., Gleason, C., Dickson, M., Altman, R. B., Batzoglou, S., Myers, R. M. (2003). Identification of Promoter Regions in the Human Genome by Using a Retroviral Plasmid Library-Based Functional Reporter Gene Assay. Genome Res 13: 1765-1774 [Abstract] [Full Text]  
  • Ramezani, A., Hawley, T. S., Hawley, R. G. (2003). Performance- and safety-enhanced lentiviral vectors containing the human interferon-{beta} scaffold attachment region and the chicken {beta}-globin insulator. Blood 101: 4717-4724 [Abstract] [Full Text]  
  • Wu, X., Li, Y., Crise, B., Burgess, S. M. (2003). Transcription Start Regions in the Human Genome Are Favored Targets for MLV Integration. Science 300: 1749-1751 [Abstract] [Full Text]  
  • Sandmeyer, S. (2003). Integration by design. Proc. Natl. Acad. Sci. USA 100: 5586-5588 [Full Text]  
  • Laufs, S., Gentner, B., Nagy, K. Z., Jauch, A., Benner, A., Naundorf, S., Kuehlcke, K., Schiedlmeier, B., Ho, A. D., Zeller, W. J., Fruehauf, S. (2003). Retroviral vector integration occurs in preferred genomic targets of human bone marrow-repopulating cells. Blood 101: 2191-2198 [Abstract] [Full Text]  
  • Jin, Y. F., Ishibashi, T., Nomoto, A., Masuda, M. (2002). Isolation and Analysis of Retroviral Integration Targets by Solo Long Terminal Repeat Inverse PCR. J. Virol. 76: 5540-5547 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»