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.

  • Letter
  • Published:

Specific incorporation of cyclophilin A into HIV-1 virions

Abstract

LITTLE is known about host factors necessary for retroviral virion assembly or uncoating. We have previously shown that the principal structural protein of the human immunodeficiency virus HIV-1, the Gag polyprotein, binds the cyclophilin peptidyl–prolyl isomerases1; cyclophilins catalyse a rate-limiting step in protein folding2 and protect cells from heat shock3. Here we demonstrate that cyclophilin A is specifically incorporated into HIV-1 virions but not into virions of other primate immunodeficiency viruses. A proline-rich region conserved in all HIV-1 Gag polyproteins is required for cyclophilin A binding and incorporation. Disruption of a single proline blocks the Gag–cyclophilin interactionin vitro, prevents cyclophilin A incorporation into virions, and inhibits H1V-1 replication. Our results indicate that the interaction of Gag with cyclophilin A is necessary for the formation of infectious HIV-1 virions.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Luban, J., Bossolt, K. A., Franke, E. K., Kalpana, G. V. & Goff, S. P. Cell 73, 1067–1078 (1993).

    Article  CAS  PubMed  Google Scholar 

  2. Fischer, G. & Schmid, F. X. Biochemistry 29, 2205–2212 (1990).

    Article  CAS  PubMed  Google Scholar 

  3. Sykes, K., Gething, M.-J. & Sambrook, J. Proc. natn. Acad. Sci. U.S.A. 90, 5853–5857 (1993).

    Article  ADS  CAS  Google Scholar 

  4. Hasel, K. W., Glass, J. R., Godbout, M. & Sutcliffe, J. G. Molec. cell. Biol. 11, 3484–3491 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Panet, A., Baltimore, D. & Hanafusa, T. J. Virol. 16, 146–152 (1975).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Myers, G., Wain-Hobson, S., Korber, B., Smith, R. F. & Pavlakis, G. N. Human Retroviruses and AIDS (Los Alamos National Laboratory, Los Alamos, 1993).

    Google Scholar 

  7. Koletsky, A. J., Harding, M. W. & Handschumacher, R. E. J. Immun. 137, 1054–1059 (1986).

    CAS  PubMed  Google Scholar 

  8. Rosenwirth, B. et al. Antimicro. Agents Chemother. 38, 1763–1772 (1994).

    Article  CAS  Google Scholar 

  9. Karpas, A., Lowdell, M., Jacobson, S. & Hill, F. Proc. natn. Acad. Sci. U.S.A. 89, 8351–8355 (1992).

    Article  ADS  CAS  Google Scholar 

  10. Luban, J. & Goff, S. J. Virol. 65, 3203–3212 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Franke, E. K., Yuan, H. E.-H., Bossolt, K. L., Goff, S. P. & Luban, J. J. Virol. 68, 5300–5305 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Jin, M. J. et al. EMBO J. 13, 2935–2947 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Friedman, J. & Weissman, I. Cell 66, 799–806 (1991).

    Article  CAS  PubMed  Google Scholar 

  14. Liu, J. et al. Cell 66, 807–815 (1991).

    Article  CAS  PubMed  Google Scholar 

  15. Adachi, A. et al. J. Virol. 59, 284–291 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Dewhurst, S., Embretson, J. E., Anderson, D. C., Mullins, J. I. & Fultz, P. N. Nature 345, 636–640 (1990).

    Article  ADS  CAS  PubMed  Google Scholar 

  17. Guyader, M. et al. Nature 326, 662–669 (1987).

    Article  ADS  CAS  PubMed  Google Scholar 

  18. Kestler, H. et al. Science 248, 1109–1112 (1990).

    Article  ADS  CAS  PubMed  Google Scholar 

  19. Kornfeld, H., Riedel, N., Viglianti, G. A., Hirsch, V. & Mullins, J. I. Nature 326, 610–613 (1987).

    Article  ADS  CAS  PubMed  Google Scholar 

  20. Bram, R. J., Hung, D. T., Martin, P. K., Schreiber, S. L. & Crabtree, G. Molec cell. Biol. 13, 4760–4769 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Schwartz, S. et al. J. Virol. 66, 7176–7182 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Cullen, B. Meth. Enzym. 152, 684–704 (1987).

    Article  CAS  PubMed  Google Scholar 

  23. Luban, J. & Goff, S. P. J. Virol. 68, 3784–3793 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Paxton, W., Connor, R. I. & Landau, N. R. J. Virol. 67, 7229–7237 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Field, J. et al. Molec cell. Biol. 8, 2159–2165 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Mammano, F., Ohagen, A., Hoglund, S. & Gottlinger, H. G. J. Virol. 68, 4927–4936 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Franke, E., Yuan, H. & Luban, J. Specific incorporation of cyclophilin A into HIV-1 virions. Nature 372, 359–362 (1994). https://doi.org/10.1038/372359a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/372359a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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