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Functional association of cyclophilin A with HIV-1 virions

Nature volume 372, pages 363–365 (1994)Cite this article

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.

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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
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  7. Heinrich G. Göttlinger
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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

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