Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

A role for LEDGF/p75 in targeting HIV DNA integration

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

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

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

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
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Manuel Llano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eric Poeschla
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christian Hoffmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jeremy Leipzig
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Paul Shinn
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Joseph R Ecker
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Frederic Bushman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Eric Poeschla or Frederic Bushman.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

GenBank and Gene Expression Omnibus accession codes. (PDF 19 kb)

Supplementary Methods (PDF 34 kb)

Rights and permissions

Reprints 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

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm1329

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing