A role for LEDGF/p75 in targeting HIV DNA integration (original) (raw)

Nature Medicine volume 11, pages 1287–1289 (2005)Cite this article

Abstract

HIV DNA integration is favored in active genes, but the underlying mechanism is unclear. Cellular lens epithelium-derived growth factor (LEDGF/p75) binds both chromosomal DNA and HIV integrase, and might therefore direct integration by a tethering interaction. We analyzed HIV integration in cells depleted for LEDGF/p75, and found that integration was (i) less frequent in transcription units, (ii) less frequent in genes regulated by LEDGF/p75 and (iii) more frequent in GC-rich DNA. LEDGF is thus the first example of a cellular protein controlling the location of HIV integration in human cells.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 12 print issues and online access

$209.00 per year

only $17.42 per issue

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Figure 1: Depleting cells of LEDGF/p75 alters the distribution of HIV integration sites in vivo.

Similar content being viewed by others

References

  1. Schroder, A. et al. Cell 110, 521–529 (2002).
    Article CAS Google Scholar
  2. Wu, X., Li, Y., Crise, B. & Burgess, S.M. Science 300, 1749–1751 (2003).
    Article CAS Google Scholar
  3. Mitchell, R. et al. PLoS Biol. 2, E234 (2004).
    Article Google Scholar
  4. Narezkina, A. et al. J. Virol. 78, 11656–11663 (2004).
    Article CAS Google Scholar
  5. Sandmeyer, S. Proc. Natl. Acad. Sci. USA 100, 5586–5588 (2003).
    Article CAS Google Scholar
  6. Bushman, F. et al. Nat. Rev. Micro. advance online publication 19 September 2005 (10.1038/nrmicro1263).
  7. Cherepanov, P. et al. J. Biol. Chem. 278, 372–381 (2003).
    Article CAS Google Scholar
  8. Turlure, F., Devroe, E., Silver, P.A. & Engelman, A. Front. Biosci. 9, 3187–3208 (2004).
    Article CAS Google Scholar
  9. Maertens, G. et al. J. Biol. Chem. 278, 33528–33539 (2003).
    Article CAS Google Scholar
  10. Llano, M. et al. J. Virol. 78, 9524–9537 (2004).
    Article CAS Google Scholar
  11. Llano, M., Delgado, S., Vanegas, M. & Poeschla, E.M. J. Biol. Chem. 279, 55570–55577 (2004).
    Article CAS Google Scholar
  12. Vanegas, M. et al. J. Cell Sci. 118, 1733–1743 (2005).
    Article CAS Google Scholar
  13. Lewinski, M. et al. J. Virol. 79, 6610–6619 (2005).
    Article CAS Google Scholar
  14. Devroe, E. & Silver, P.A. BMC Biotechnol. 2, 15 (2002).
    Article Google Scholar
  15. Cherepanov, P., Devroe, E., Silver, P.A. & Engelman, A. J. Biol. Chem. 279, 48883–48892 (2004).
    Article CAS Google Scholar
  16. Ge, H., Si, Y. & Roeder, R.G. EMBO J. 17, 6723–6729 (1998).
    Article CAS Google Scholar

Download references

Acknowledgements

We thank P. Bates, C. Berry, R. Doms, S. Hannenhalli and members of the Bushman, Ecker and Poeschla laboratories for discussions and M. Vanegas for help with the LEDGF/p75 knockdown cell lines. This work was supported by US National Institutes of Health grants AI52845 and AI34786, the J.B. Pendleton Charitable Trust, and R. and F. Withington (to F.B.) and the F.B. Burns Foundation (to J.R.E.) and AI47536 (to E.P.). A.C. was supported in part by a fellowship from the Swiss National Science Foundation.

Author information

Authors and Affiliations

  1. Department of Microbiology, University of Pennsylvania School of Medicine, 3610 Hamilton Walk, Philadelphia, 19104-6076, Pennsylvania, USA
    Angela Ciuffi, Christian Hoffmann, Jeremy Leipzig & Frederic Bushman
  2. Molecular Medicine Program, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, 55905, Minnesota, USA
    Manuel Llano & Eric Poeschla
  3. Genomic Analysis Laboratory, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, 92037, California, USA
    Paul Shinn & Joseph R Ecker

Authors

  1. Angela Ciuffi
    You can also search for this author inPubMed Google Scholar
  2. Manuel Llano
    You can also search for this author inPubMed Google Scholar
  3. Eric Poeschla
    You can also search for this author inPubMed Google Scholar
  4. Christian Hoffmann
    You can also search for this author inPubMed Google Scholar
  5. Jeremy Leipzig
    You can also search for this author inPubMed Google Scholar
  6. Paul Shinn
    You can also search for this author inPubMed Google Scholar
  7. Joseph R Ecker
    You can also search for this author inPubMed Google Scholar
  8. Frederic Bushman
    You can also search for this author inPubMed Google Scholar

Corresponding authors

Correspondence toEric Poeschla or Frederic Bushman.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Rights and permissions

About this article

Cite this article

Ciuffi, A., Llano, M., Poeschla, E. et al. A role for LEDGF/p75 in targeting HIV DNA integration.Nat Med 11, 1287–1289 (2005). https://doi.org/10.1038/nm1329

Download citation

This article is cited by