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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.

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

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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

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
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  2. Manuel Llano
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  3. Eric Poeschla
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  4. Christian Hoffmann
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  5. Jeremy Leipzig
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  6. Paul Shinn
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  7. Joseph R Ecker
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  8. Frederic Bushman
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Corresponding authors

Correspondence to Eric Poeschla or Frederic Bushman.

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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)

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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

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