Skip to main content

Advertisement

SpringerLink
Log in

Functional association of cyclophilin A with HIV-1 virions

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

Abstract

CYCLOPHILINS are a family of proteins that bind the immunosuppressant cyclosporin A, possess peptidyl–prolylcis–trans isomerase activity, and assist in the folding of proteins1–6. Human cyclophilins A and B are host cell proteins that bind specifically to the HIV-1 Gag polyprotein p55gag in vitro7. Here we report that viral particles formed by p55gag, in contrast to particles formed by the Gag polyproteins of other retroviruses, contain significant amounts of cyclophilin A. Sequences in the capsid domain of p55gag are both required and sufficient for the virion-association of cyclophilin A. The association of cyclophilin A with HIV-1 virions was inhibited in a dose-dependent manner by cyclosporin A as well as by SDZ NIM811 ([Melle-4]cyclosporin), a non-immunosuppressive analogue of cyclosporin A8. Drug-induced reductions in virion-associated cyclophilin A levels were accompanied by reductions in virion infectivity, indicating that the association is functionally relevant. Moreover, SDZ NIM811 inhibited the replication of HIV-1 but was inactive against SIVMAC, a primate immunodeficiency virus closely related to HIV-1, which does not incorporate cyclophilin A.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Handschumacher, R. E., Harding, M. W., Rice, J., Drugge, R. J. & Speicher, D. W. Science 226, 544–546 (1984).

    Article  ADS  CAS  PubMed  Google Scholar 

  2. Takahashi, N., Hayano, T. & Suzuki, M. Nature 337, 473–475 (1989).

    Article  ADS  CAS  PubMed  Google Scholar 

  3. Fischer, G., Wittmann-Liebold, B., Lang, K., Kiefhaber, T. & Schmid, F. X. Nature 337, 476–478 (1989).

    Article  ADS  CAS  PubMed  Google Scholar 

  4. Schreiber, S. L. Science 251, 283–287 (1991).

    Article  ADS  CAS  PubMed  Google Scholar 

  5. Walsh, C. T., Zydowsky, L. D. & McKeon, F. D. J. biol. Chem. 267, 13115–13118 (1992).

    CAS  PubMed  Google Scholar 

  6. Stamnes, M. A., Rutherford, S. L. & Zuker, C. S. Trends Cell Biol. 2, 272–276 (1992).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Göttlinger, H. G., Sodroski, J. G. & Haseltine W. A. Proc. natn. Acad. Sci. U.S.A. 86, 5781–5785 (1989).

    Article  ADS  Google Scholar 

  10. Gelderblom, H. R., Hausmann, E. H., Özel, M., Pauli, G. & Koch, M. A. Virology 156, 171–176 (1987).

    Article  CAS  PubMed  Google Scholar 

  11. Mammano, F., Öhagen, A., Höglund, S. & Göttlinger, H. G. J. Virol. 68, 4927–4936 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Wills, J. W. & Craven, R. C. AIDS 5, 639–654 (1991).

    Article  CAS  PubMed  Google Scholar 

  13. Helseth, E. et al. J. Virol. 64, 2416–2420 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Gelderblom, H., Reupke, H., Winkel, T., Kunze, R. & Pauli, G. Z. Naturforschung 42c, 1328–1334 (1987).

    Article  CAS  Google Scholar 

  15. Kannagi, M., Kiyotaki, M., King, N. W., Lord, C. I. & Letvin, N. L. J. Virol. 61, 1421–1426 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Arthur, L. O. et al. Science 258, 1935–1938 (1992).

    Article  ADS  CAS  PubMed  Google Scholar 

  17. Schols, D., Pauwels, R., Desmyter, J. & De Clercq, E. Virology 189, 374–376 (1992).

    Article  CAS  PubMed  Google Scholar 

  18. Kaye, R. E. et al. Proc. natn. Acad. Sci. U.S.A. 89, 8542–8546 (1992).

    Article  ADS  CAS  Google Scholar 

  19. Dorfman, T., Mammano, F., Haseltine, W. A. & Göttlinger, H. G. J. Virol. 68, 1689–1696 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Göttlinger, H. G., Dorfman, T., Cohen, E. A. & Haseltine, W. A. Proc. natn. Acad. Sci. U.S.A. 90, 7381–7385 (1993).

    Article  ADS  Google Scholar 

  21. Terwilliger, E. F., Godin, B., Sodroski, J. G. & Haseltine, W. A. Proc. natn. Acad. Sci. U.S.A. 86, 3857–3861 (1989).

    Article  ADS  CAS  Google Scholar 

  22. Dayton, A. I., Sodroski, J. S., Rosen, C. A., Goh, W. C. & Haseltine, W. A. Cell 44, 941–947 (1986).

    Article  CAS  PubMed  Google Scholar 

  23. Dorfman, T., Bukovsky, A., Öhagen, Å., Höglund, S. & Göttlinger, H. G. J. Virol. 68, 8180–8187 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Author notes

  1. Markus Thali

    Present address: Institute of Microbiology, University of Lausanne, CH-1066, Epalinges, Switzerland

Authors and Affiliations

  1. Division of Human Retrovirology, Dana-Farber Cancer Institute,

    Markus Thali, Anatoly Bukovsky, Eisaku Kondo, Joseph Sodroski & Heinrich G. Göttlinger

  2. Department of Pathology, Harvard Medical School, Boston, Massachusetts, 02115, USA

    Markus Thali, Anatoly Bukovsky, Eisaku Kondo, Joseph Sodroski & Heinrich G. Göttlinger

  3. SANDOZ Forschungsinstitut GmbH, A-1235, Vienna, Austria

    Brigitte Rosenwlrth

  4. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, 02115, USA

    Christopher T. Walsh

Authors
  1. Markus Thali
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anatoly Bukovsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eisaku Kondo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Brigitte Rosenwlrth
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christopher T. Walsh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Joseph Sodroski
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Heinrich G. Göttlinger
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Thali, M., Bukovsky, A., Kondo, E. et al. Functional association of cyclophilin A with HIV-1 virions. Nature 372, 363–365 (1994). https://doi.org/10.1038/372363a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/372363a0

  • Springer Nature Limited

This article is cited by

Search

Navigation