A role for LEDGF/p75 in targeting HIV DNA integration (original) (raw)
- Brief Communication
- Published: 27 November 2005
- Manuel Llano2,
- Eric Poeschla2,
- Christian Hoffmann1,
- Jeremy Leipzig1,
- Paul Shinn3,
- Joseph R Ecker3 &
- …
- Frederic Bushman1
Nature Medicine volume 11, pages 1287–1289 (2005)Cite this article
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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.
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Authors and Affiliations
- 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 - Molecular Medicine Program, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, 55905, Minnesota, USA
Manuel Llano & Eric Poeschla - Genomic Analysis Laboratory, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, 92037, California, USA
Paul Shinn & Joseph R Ecker
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Correspondence toEric Poeschla or Frederic Bushman.
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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
- Received: 08 June 2005
- Accepted: 21 October 2005
- Published: 27 November 2005
- Issue Date: 01 December 2005
- DOI: https://doi.org/10.1038/nm1329