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A role for LEDGF/p75 in targeting HIV DNA integration

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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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.

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Correspondence to Eric 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

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