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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

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

References

  1. 1

    Schroder, A. et al. Cell 110, 521–529 (2002).

  2. 2

    Wu, X., Li, Y., Crise, B. & Burgess, S.M. Science 300, 1749–1751 (2003).

  3. 3

    Mitchell, R. et al. PLoS Biol. 2, E234 (2004).

  4. 4

    Narezkina, A. et al. J. Virol. 78, 11656–11663 (2004).

  5. 5

    Sandmeyer, S. Proc. Natl. Acad. Sci. USA 100, 5586–5588 (2003).

  6. 6

    Bushman, F. et al. Nat. Rev. Micro. advance online publication 19 September 2005 (10.1038/nrmicro1263).

  7. 7

    Cherepanov, P. et al. J. Biol. Chem. 278, 372–381 (2003).

  8. 8

    Turlure, F., Devroe, E., Silver, P.A. & Engelman, A. Front. Biosci. 9, 3187–3208 (2004).

  9. 9

    Maertens, G. et al. J. Biol. Chem. 278, 33528–33539 (2003).

  10. 10

    Llano, M. et al. J. Virol. 78, 9524–9537 (2004).

  11. 11

    Llano, M., Delgado, S., Vanegas, M. & Poeschla, E.M. J. Biol. Chem. 279, 55570–55577 (2004).

  12. 12

    Vanegas, M. et al. J. Cell Sci. 118, 1733–1743 (2005).

  13. 13

    Lewinski, M. et al. J. Virol. 79, 6610–6619 (2005).

  14. 14

    Devroe, E. & Silver, P.A. BMC Biotechnol. 2, 15 (2002).

  15. 15

    Cherepanov, P., Devroe, E., Silver, P.A. & Engelman, A. J. Biol. Chem. 279, 48883–48892 (2004).

  16. 16

    Ge, H., Si, Y. & Roeder, R.G. EMBO J. 17, 6723–6729 (1998).

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

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

Further reading